Shigella 620 Infection is generally limited to the intestinal mucosa and involves a possible enterotoxic or cytoxic diarrhoeal prodrome, cytokine-mediated inflammation of the colon, and necrosis of the colonic epithelium. This inflammation is caused by the invasion of Shigella into the colonic epithelium and the lamina propria. Shigella can enter both M cells and enterocytes, reorganizing the cytoskeleton, beginning with the type II secretion system. The colitis and ulceration of the mucosa result in febrile diarrhoea and/or bloody, mucoid stools (Niyogi, 2005). Shigella strains produce three distinct enterotoxins: (i) chromosome encoded shigella enterotoxin 1 (SHET1) which is present in all S. flexneri 2a but rarely found in other shigella serotypes. This toxin is enterotoxic, neurotoxic, and cytoxic, with a structure simlilar to the Shiga-like toxins of enterohaemorrhagic E. Coli infection. The toxin is not essential for virulence, but does contribute to the severity of disease manifestations. Also, this toxin adheres to the small intestine receptors and blocks electrolyte, glucose, and amino acid absorption from the intestinal lumen. The B subunit of this toxin binds host cell glycolipid in the large intestine, A1 domain internalized via receptor-mediated endocytosis and causes irreversible inactivation of the 60S ribosomal subunit, inhibiting protein synthesis, causing cell death, microvasculature damage to the intestine, and haemorrhage. (ii) shigella enterotoxin 2 (SHET2), which is located on a large plasmid associated with the virulence of shigella. SHET2 was found in many shigella of different serotypes and also in enteroinvasive E. coli. Inactivation of SHET1 and SHET2 through genetic engineering is used for attenuation of new shigella vaccine candidates. (iii) phage-born Shiga toxin by S. dysenteriae (Niyogi, 2005). Shigellosis Wild type Shigella infection induces protective immunity, which develops after repeated exposure during childhood. This immunity is serotype specific (e.g., directed to the LPS O antigen of this organism). Shigella antigen specific antibody response develops early in infection and follows the typical course for anti-LPS antibodies, that is, an IgM response that peaks within weeks of exposure and wanes after 1-2 year (Niyogi, 2005). Humans are the only natural host for Shigella, but NHP have also been used in vaccine trials (Niyogi, 2005). Shigellosis is caused by Shigella species. It is an important public health problem, espcially in countries with unsafe water supplies and substandard hygiene. The morbidity and mortality due to shigellosis are especially high among children in these developing countries, causing a cycle of impaired nutrition, recurrent infection, and the retardation of growth. The predominant role of transmission is through faecal-oral contact. Shigellosis is characterized by diarrhoea and/or dysentery with frequent bloody, mucoid stools, tenesmus, and abdominal cramps. Shigella is an uncapsulated, non-motile Gram negative nonsporulating , facultative anaerobic bacilli. Four species of Shigella are able to cause disease: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. Each of these species are subdivided into serotypes based on their O-specific polysaccharide of the LPS. A variety of antimicrobial agents are effective for the treatment of shigellosis, but options are becoming limited as a result of global drug resistance. Quinolone was one of the preferred agents for treatment of Shigella in the 1990s. New vaccine development has been hampered by three factors: (i) the ineffectiveness of parenterally injected inactivated whole-cell vaccines which led to the belief that serum antibodies do not confer immunity; (ii) the lack of suitable animal model; (iii) only indirect evidence of immune mechanisms in humans (Niyogi, 2005). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 CVD 1204(pGA1-CS2) VO_0000733 Live, attenuated vaccine This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) CS2 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 10^9 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001). Recombinant protein preparation Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA, whereas three-fourths of the animals responded with anti-Shigella LPS serum IgG. All animals immunized with CVD 1204(pGA1-CS2) (groups 3 and 4) developed anti-CS2 mucosal IgA and serum IgG following a single dose. Two immunizations were required to elicit anti-CS2 serum IgG responses in all animals (Altboum et al., 2001). Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 10^9 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 10^10 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001). CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001). Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS2) had a score of 1 on day 3. One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001). Conjuntivitis (Altboum et al., 2001). The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 10^8 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001). Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA. After second immunization, the most dramatic difference in IgA titers between pre and post immunization was seen in guinea pigs (Altboum et al., 2001). Following a single dose of any CVD 1204 inoculum, three-fourths of the animals responded with anti-Shigella LPS serum IgG. A dramatic increase in IgG titers between pre and post immunized guinea pigs was seen after the second immunization (Altboum et al., 2001). CVD 1204(pGA1-CS3) VO_0000734 Live, attenuated vaccine Licensed Intramuscular injection (i.m.) This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) ETEC CS3 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 10^9 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001). Intramuscular injection (i.m.) Animals immunized with Shigella expressing CS3 developed serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the homologous fimbriae (Altboum et al., 2001). Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 10^9 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 10^10 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001). CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001). Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001). Conjuntivitis (Altboum et al., 2001). The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 10^8 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001). CVD 1208 VO_0000666 Live, attenuated vaccine Licensed Intramuscular injection (i.m.) Attenuated (Kotloff et al., 2004). CVD 1208 is derived from wild type Shigella flexneri 2a strain 2457T and has defined deletions in four genes: (1) the guaBA chromosomal operon that encodes two enzymes (inositol 5'-monophosphate dehydrogenase and guanosine 5'synthase) essential for de novo purine biosynthesis; (2) set, a locus in a chromosomal pathogenicity island that encodes Shigella enterotoxin (ShET); (3) Pic, an autotransporter mucinase encoded on the opposite strand from set; and (4) sen, an invasiveness plasmid gene encoding ShET (Kotloff et al., 2004). Intramuscular injection (i.m.) CVD 1208S VO_0000668 Live, attenuated vaccine CVD 1208S is the same thing as CVD 1208, but CVD 1208S was prepared using animal-free media (Kotloff et al., 2007). The inocula were derived from frozen master cell banks containing prepared strains of CVD 1208S. Frozen master seed was plated onto SP agar. After incubation, several Congo Red-dyed colonies proven to be Shigella were suspended in sterile saline. This saline was used to inoculate SP plates for the heavy bacterial growth. These resulting colonies were harvested into PBS and diluted to the appropriate bacterial count, which was between 1 x 10^8 and 1 x 10^9 CFU per ml (Kotloff et al., 2007). The antigen for this vaccine is CVD 1208s, which is Shigella flexneri containing deletions in sen, set, and guaBA (Kotloff et al., 2007). Following vaccination, all subjects mounted an anti-LPS IgA ASC response and 5 exhibited an anti-LPS IgG ASC response. Anti-LPS responses typically reached a peak on Day 14. Some volunteers exhibited a serum antibody response to Ipa and IpaB. All recipients of the higher dose (1 x 10^9 CFU) demonstrated a response in two or more of the immunologic assays (Kotloff et al., 2007). 16 volunteers were assigned to receive between 1 x 10^8 and 1 x 10^9 CFU per ml of CVD 1208S or a placebo. Volunteers ingested a buffer solution, then ingested 1 ml of vaccine or placebo suspended in 30 ml of buffer solution. Vaccine excretion was monitered through the culture of all stools and through collection of blood samples (Kotloff et al., 2007). Vaccine was detected in the stool of all volunteers that received the 1 x 10^9 CFU dosage for at least one day. The same was true for six of the volunteers that received 1 x 10^8 CFU, with no vaccine detected in the volunteers that received the placebo. Peak excretion occurred on Day 1 and total excretion did not exceed the dosage levels (Kotloff et al., 2007). Side effects included mucoid or loose stools and fever, in some cases (Kotloff et al., 2007). EcSf2a-2 VO_0000670 Recombinant vector vaccine Vaccinated monkeys were protected against shigellosis after challenge with S. flexneri 2a (Kotloff et al., 1992). The vaccine was suspended in 20 ml of BHI broth and contained 1.5 x 10^11 CFU of bacteria (Kotloff et al., 1992). This vaccine is an aro-D mutant derivative of EcSf2a-1 (Kotloff et al., 1992). A fourfold increase in IgA or IgG antibody titers recognizing purified LPS was detected in 61% of those tested, and a seroresponse to IPA was detected in 44% of the 38 recipients of ca. 2.0 x 10^9 CFU. The IgM response was meager. Circulating IgA ASC specific for S. flexneri 2a LPS and for IPA were each detected in 97% and 60%, respectively, of the 30 subjects tested (Kotloff et al., 1992). 19 volunteers ingested three doses of either ca. 5.0 x 10^6, 5.0 x 10^7, or 2.0 x 10^9 CFU of bacteria (Kotloff et al., 1992). All 46 vaccine recipients excreted the vaccine strain on at least one occasion. Recipients of three spaced doses of ca. 2.0 x 10^9 CFU shed ca. 10^5 organisms per gram of stool for an average of 7 days. Duodenal colonization was detected in five subjects, all recipients of ca. 2.0 x 10^9 CFU (Kotloff et al., 1992). Vaccine efficacy was only 9% in the challenge study, in which 30% of recipients of three doses of ca. 2.0 x 10^9 CFU developed illness, compared 33% of 9 unvaccinated control subjects. Overall, the vaccine efficacy was 36%. Neither class-specific titers in prechallenge sera nor fourfold rises in antibody titer after vaccination could be correlated with protection against challenge (Kotloff et al., 1992). Diarrhea, dysentery, and fever were observed in vaccine recipients (Kotloff et al., 1992). Challenge doses of 1.6 x 10^9 and 1.8 x 10^9 CFU of ECSf2a-2 were given to the volunteers (Kotloff et al., 1992) . Heat-killed Virulent Shigella flexneri 2a VO_0000672 Inactivated or "killed" vaccine Protection from diarrhea and dysentary following oral immunization was 100% . Each vacccine consisted of 10 ml of heat-killed bacteria, and each contained 10^11 CFU of bacteria (Chakrabarti et al., 1999). Heat-killed shigella flexneri strain 2a (Chakrabarti et al., 1999). The immune response can only be speculated upon, but it is believed that protective immunity to Shigella may by conferred by serum IgG antibodies to the O-specific polysaccaride of their lipopolysaccarides. There is also evidence that infection also confers type-specific immunity to LPS (Chakrabarti et al., 1999). New Zealand white 25 male New Zealand white rabbits were given 10 ml of broth culture containing 10^11 CFU of the heat-killed bacteria. The vaccines were administered through injection of the colon. The rabbits were imminized for seven days, and were administered a total of 5 doses (Chakrabarti et al., 1999). Not noted. Challenge was only demonstrated using the same strain present inthe vaccine, and was eveidenced by lack of diarrhea. Death following challenge was 2.5 fold higher for non-immunized rabbits, but this was not significant (Chakrabarti et al., 1999). Side effects included bloody diarrhea and dysentary (Chakrabarti et al., 1999). Challenge specifics were not specifically noted. licensed Shigellosis human vaccine Generic Unknown VO_0000769 Live, attenuated vaccine Licensed A generic representation of vaccines utilized to prevent Shigellosis in humans, most commonly based on live, attenuated Shigella strains. These vaccines aim to induce protective immunity by mimicking natural infection without causing disease. Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen VO_0000674 Recombinant vector vaccine The vaccine was demonstrated to be immunogenic in animal models, leading to 47% full protection and 53% partial protection against challenge with the wild-type strain (Klee et al., 1997). S. flexneri SFL124-27 is a spontaneous rough mutant of the attenuated S. flexneri auxotrophic strain SFL124, which carries a deletion of the aroD gene. A recombinant strain SFL124-27 that expresses S. dysenteriae 1 O antigen was selected as the vaccine candidate (Klee et al., 1997). None of the four immunization doses given to the 15 guinea pigs resulted in detectable keratoconjunctivitis, thereby demonstrating the safety of this prototype vaccine candidate in this animal model (Klee et al., 1997). Dunkin Hartley The Sereny test with guinea pigs was performed as follows: Congo red-positive colonies of the Shigella vaccine candidate were diluted in PBS, and 25 ml was applied to the conjunctival sacs of 15 adult Dunkin Hartley guinea pigs at days 0, 7, 14, and 21 with an average of four immunizing doses, 3.7 x 10^9 bacteria per eye (Klee et al., 1997). Vaccination led to statistically significant amounts of antibodies against S. Dysenteriae (Klee et al., 1997). In the vaccinated group, 7 of 15 animals developed no signs of keratoconjunctivitis (47% full protection), and in the other 8 animals, later development of the disease was observed (53% partial protection), resulting in a combined protection of 100%, whereas in the nonvaccinated group 71% of challenged animals rapidly developed severe disease.The vaccinated animals developed symptoms of keratoconjunctivitis later than animals of the control group, and the absolute number of guinea pigs showing strong reactions, or purulent inflammation of the whole eye, was significantly reduced (Klee et al., 1997). At day 35, the animals were challenged with 10^8 bacteria of the virulent strain S. dysenteriae 1 W30864 per eye, and the symptoms of keratoconjunctivitis were recorded for 6 days. As a control, another group of 14 nonvaccinated guinea pigs was also challenged with the virulent strain at day 35 (Klee et al., 1997). BALB/c To assess whether the recombinant O antigen was immunogenic and to compare the immunogenicity with that of wild-type S. dysenteriae 1, groups of five six-week-old female BALB/c mice were immunized on days 0, 14, and 28 by intraperitoneal injection of 0.2 x 10^8 to 1.0 x 10^8 heat-killed bacteria suspended in PBS. Two weeks after the last immunization, the mice were sacrificed, blood samples were collected, and antibody titers against LPS of S. dysenteriae 1 were determined by enzyme-linked immunosorbent assay (Klee et al., 1997). The antibody titers of mice immunized with S. dysenteriae 1 or S. flexneri SFL124-27::Tn(rfp-rfb)-39 were significantly higher than the titers in the nonimmunized group and in mice immunized with the rough strain SFL124-27. This indicates the synthesis of enough surface-displayed LPS molecules to trigger a specific immune response, a prerequisite for a vaccine strain (Klee et al., 1997). No challenge was done on the mice, as this was only to assess the immunogenicity of the recombinant O antigen. S. dysenteriae 1 strain WRSd1 VO_0000676 Live, attenuated vaccine Vaccination with WRSd1 conferred protection against challenge with each of three virulent S. dysenteriae 1 strains (Venkatesan et al., 2002). Attenuated S. dysenteriae 1 strain WRSd1 is a attenuated vaccine that contains deletions of the virG(icsA) gene required for intercellular spreading and a 20-kb chromosomal region encompassing the Shiga toxin genes (stxAB) (Venkatesan et al., 2002). The vaccine was made with bacterial culture grown overnight on LB agar plates and harvested in PBS (Venkatesan et al., 2002). Gene mutation WRSd1 was constructed from S. dysenteriae 1 strain 1617. The virG(icsA) deletion was constructed from a streptomycin-resistant mutant of 1617 by a filter mating procedures using a virG(icsA) deletion derivative, p
virG2. A colony that was invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting was grown anaerobically on plates containing chlorate for selection of resistant colonies that had lost the entire Shiga toxin gene. A virG(icsA) stxAB Str^r mutant selected from the chlorate plates was designated WRSd1 (Venkatesan et al., 2002). Four monkeys showed a 2-to 3-fold rise in serum immunoglobulin G (IgG) response to S. dysenteriae 1 LPS at day 7 or day 14 and one monkey showed a 3-fold rise in serum IgA responseto S. dysenteriae LPS. None of the monkeys had a detectable rectal lavage sample immune response (Venkatesan et al., 2002). Rhesus (Macaca mulatta) Five rhesus monkeys were a part of the study. 20 ml of saturated sodium bicarbonate was administered intragastrically through a pediatric stomach tube fitted over a disposable plastic syringe, followed by 20 ml of the bacterial inoculum (10^9 CFU) of WRSd1) in water. The inoculum was obtained by hydrating the lyophilized vaccine product (Venkatesan et al., 2002). Two of five monkeys excreted the vaccine strain in stool cultures for 48 h after the administration of the vaccine, as evidenced by transparent colonies on Hektoen agar plates (Venkatesan et al., 2002). The immune response generated was higher than that observed in monkeys given 6 x 10^9 CFU of the cGMP product (Venkatesan et al., 2002). Not noted. Monkeys were challenged with 2 x 10^10 CFU of SC602 vaccine (Venkatesan et al., 2002). Not noted. The eyes of 12 guinea pigs were inoculated with 10^8 CFU of WRSd1. The eyes were observed for 5 to 6 days for evaluation of the Sereny reaction. When eyes were immunized for efficacy studies of vaccine candidates, mmunization was carried out twice at 2-week intervals (Venkatesan et al., 2002). WRSd1 protected fully against challenge by Ubon 378 and Shiga. At the single dose used for immunization in this experiment, WRSd1 protected partially against the parent strain 1617 (Venkatesan et al., 2002). Side effects included purulence and conjunctivitis in some of the eyes tested (Venkatesan et al., 2002). Four weeks after the last immunization, animals were challenged at the same dose using one of three virulent S. dysenteriae 1 strains: 1617, the parent strain of WRSd1; Ubon 378; and Shiga (Venkatesan et al., 2002). S. flexneri Invaplex 24 Subunit Vaccine VO_0011466 Subunit vaccine Research Intranasally Isolated invasin complex (invaplex), which contains the major antigens of virulent Shigella, is shown to be immunogenic when delivered by a mucosal route without the need for any additional adjuvant. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. (Turbyfill et al., 2000) A novel method has been developed for isolating a macromolecular complex containing the major known virulence factors and immunogens from intact, viable, virulent shigellae. This structure was referred as the invasin complex, or invaplex. It has been possible to isolate two forms of the invaplex, called invaplex 24 and invaplex 50, by FPLC ion-exchange chromatography from S. flexneri 2a and S. flexneri 5. Both forms contain the invasins (IpaB, IpaC, and IpaD) and LPS, but IpaA and VirG, a truncated form of VirG, were found only in Invaplex 50. Other unidentified proteins were also present in both invaplex preparations (Turbyfill et al., 2000). Intranasally IpaB, IpaC, and IpaD, and LPS (Turbyfill et al., 2000). Recombinant protein preparation Recombinant protein preparation Recombinant protein preparation BALB/cByJ The ability of the invaplex fractions to promote an immune response in BALB/cByJ mice was tested in groups of five mice. Each mouse was immunized intranasally with 5 μg of invaplex 24 or invaplex 50 from S. flexneri 2a or S. flexneri 5 on days 0, 14, and 28. Saline was used to immunize control animals. A total antigen volume of 25 μl was delivered in 5 to 6 small drops applied to the external nares with a micropipette (Turbyfill et al., 2000). A significant level of protection against lethal challenge was achieved in mice immunized with S. flexneri 2a invaplex 24. Invaplex-immunized mice lost weight upon challenge, but by days 3 to 4 they began to recover and gain weight whereas control mice soon died. Similar levels of protection were afforded by invaplex 24 (12 of 15 mice survived). Three weeks after the final immunization with either S. flexneri 2a invaplex 24, invaplex 50, or saline, mice (15 per group) were challenged intranasally with a lethal dose of S. flexneri 2a 2457T (10^7 CFU/30 μl) as described for the mouse lung model. The mouse challenge dose was prepared from a frozen lot of S. flexneri 2a that had been harvested during the log phase of growth, which is the time of optimal invasiveness for shigellae, and then stored in liquid nitrogen (Turbyfill et al., 2000). S. flexneri 2a LPS vaccine complexed with N. meningitidis proteosomes VO_0000682 Subunit vaccine Strong anamnestic responses were found , so acellular Shigella vaccines can protect against Shigella infection (Orr et al., 1993). Purified shigella LPS and group C serotype 2b N. meningitidis outer membrane proteins were mixed at a 1:1 ratio in PBS containing 1% Empigen. The mixture was dialyzed across a dialysis membrane against PBS. Samples of the purified LPS were mixed with PBS and sodium bicarbonate (Orr et al., 1993). The antigen for this acellular vaccine is purified Shigella flexneri LPS (Orr et al., 1993). Vaccination produced high levels of anti-LPS IgG and anti-LPS IgA in mice immunized two or three times (Orr et al., 1993). BALB/c BALB/c mice were were immunized either orally or intranasally with 100 miroliters of PBS containing 100 micrograms of LPS with 0.2 M sodium bicarbonate that was given either alone or complexed with 100 micrograms of proteosomesusing a bent metal tube. For intranasal immunization, 25 micrograms of LPS either alone or complexed with 10 micrograms of proteosomeswas slowly placed into one or both of the nares. The control group recieved diluent without antigen (Orr et al., 1993). All mice in control groups were infected. 14 out of 19 and 11 out of 16 mice were protected from severe infection after intranasal or oral vaccination. 9 out of 16 animals were protected from any illness (Orr et al., 1993). Mice were challenged with LPS two weeks after their last immunization (Orr et al., 1993). Guinea pig titers proved strong anti-LPS IgG antibodies and anti-LPS IgA antibodies (Orr et al., 1993). DH Anesthetized guinea pigs were immunized. Orally, they each received 200 microliters of PBS with sodium bicarbonate and 200 micrograms of the LPS complex. Intranasally, each guinea pig received 50 microliters of PBS with 40 micrograms of the LPS complex (Orr et al., 1993). The vaccines elicited an in vivo protection against homologous bacteria (Orr et al., 1993). The conjunctival sac of one eye of each animal was inoculated with 30 microliters of a suspension containing and estimeted 10^8 of homologous bacteria (Orr et al., 1993). S. flexneri 2a strain CVD 1203 VO_0002920 Recombinant vector vaccine Two 10^9-CFU orogastric doses (2 weeks apart) stimulated production of secretory immunoglobulin A antibodies to S.flexneri 2a and protected against conjunctival sac challenge with virulent S. flexneri 2a. The antigen for this vaccine is S. flexneri 2a strain 1203, a strain which contains deletions in chromosomal aroA and invasion plasmid virG (Noriega et al., 1994). Recombinant protein preparation Noriega et al. sequentially introduced precise deletion mutations into chromosomal gene aroA and plasmid gene virG in a wild-type S. flexneri 2a strain known to be virulent in volunteers. In order to do this, they constructed aroA and introduced several deletion cassetes (Noriega et al., 1994). Immunization with CVD 1203 clearly stimulated production of S-IgA antibodies to S. flexneri 2a LPS in tears (Noriega et al., 1994). Hartley 33 guinea pigs were randomly allocated to receive orogastrically 10 CFU of CVD 1203 or control strain E. coli HS. A second immunization was given 15 days later. Tears were collected from 10 guinea pigs (5 immunized with CVD 1203 and 5 immunized with E. coli HS) on days 7, 14, and 21 after the first orogastric dose to measure secretory immunoglobulin A (S-IgA) antibodies against S. flexneri 2a LPS by enzyme-linked immunosorbent assay (Noriega et al., 1994). Full-blown keratoconjunctivitis developed in 16 of 17 control animals orogastrically vaccinated with the placebo (a 94% attack rate), in contrast to only 3 of 16 guinea pigs immunized with two spaced orogastric doses of CVD 1203 (a 19% attack rate) (Noriega et al., 1994). Not noted. On the 28th day after the first immunization, 16 vaccinated guinea pigs and 17 control guinea pigs were challenged with 5 x 10^7 CFU of the wild-type 2457T strain in 10 ,ul (Noriega et al., 1996). Immunization with CVD 1203 clearly stimulated production of IgA antibodies to S. flexneri 2a LPS in tears. A significant increase was seen 14 days after immunization, which was compared to the static control immunization with E. coli HS (Noriega et al., 1994). S. flexneri 2a strain CVD 1205 VO_0004143 Recombinant vector vaccine Upon Sereny test challenge with wild-type S. flexneri 2a, CVD 1205-vaccinated animals were significantly protected against keratoconjunctivitis (Noriega et al., 1996). Overnight cultures of guaB-A virG S. flexneri 2a strain CVD 1205 and HS strains were harvested and resuspended PBS to an optical density at 600 nm of 0.5 (equivalent to 5 3 10^8 CFU/ml) and concentrated by centrifugation to the desired concentration (Noriega et al., 1996). The antigen for this vaccine is S. flexneri 2a strain CVD 1205, which carries deletion mutations in the guaB-A operon and in the virG gene (also called icsA) (Noriega et al., 1996). Recombinant protein preparation CVD 1205 is made through deletion of virG from CVD 1204. Producing strain CVD 1205 took many steps and began with construction of the guaB-A deletion cassette pFM726A. In the construction of the guaB-A deletion cassette, DNA segments that included the 59 terminus of guaB and the 39 terminus of guaA were amplified (from S. flexneri 2a strain 2457T genomic DNA) and fused by PCR, originating the guaB-A allele. With the internal primers (primers 2 and 3) was introduced an in-frame stop sign upstream of two unique restriction sites that were added for the future introduction of foreign genes into the chromosomal DguaB-A allele. The external primers (primers 1 and 4) were designed to introduce unique restriction sites that were used to clone the guaB-A allele into the temperature-sensitive, pSC101-based suicide plasmid pFM307A, originating pFM726A. The same external primers were used to amplify the wild-type guaB-A operon (from strain 2457T), which was subsequently cloned in pGEM-T, yielding pGEM::gua, and in pFM307A, yielding pFM215A. Suicide cassette-driven deletion mutations and repair of the same. Deletion cassette pFM726A was used to introduce the deletion mutation into wild-type S.flexneri 2a strain 2457T by homologous recombination as described in previously published method, yielding strain CVD 1204. Plasmid FM215A was used to repair the deletion mutation by homologous recombination of the chromosomal guaB-A allele in strain CVD 1204 for the wild-type operon contained in the suicide plasmid. A second deletion mutation on the virulence gene virG was performed with a previously described suicide deletion cassette (pDvirG) and methods (24), yielding strain CVD 1205. The deletion mutation corresponds to 900 bases representing amino acids 341 to 640 of the 120-kDa VirG protein. The specific engineered site for this deletion in the protein represents a highly hydrophobic, poorly antigenic portion of the molecule genic index (Noriega et al., 1996). The serum antibody response was more delayed, since no serum IgG or IgA anti-Shigella LPS was detected after the first immunization. However, by day 2 animals immunized with CVD 1205 had specific anti-S. flexneri 2a LPS IgA (i.e., 78-fold rise in GMT) and IgG (i.e., 60-fold rise in GMT) titers that were highly significant with respect to those obtained at day 0 in the same guinea pigs or at days 0 and 28 in the strain HS controls (Noriega et al., 1996). Hartley Randomized, nonpreconditioned Hartley guinea pigs were given intranasally 100 ml of bacterial suspension containing 10^9 CFU as described previously. A booster dose was administered 14 days later in the identical manner (Noriega et al., 1996). At 72 h postinoculation, the (blinded) observer grading the inflammatory response in the guinea pigs could not distinguish the inoculated eye from the noninoculated one in any of the animals that received the attenuated mutant CVD 1205, while all animals that received wild-type strain 2457T had full-blown purulent keratoconjunctivitis (Noriega et al., 1996). Full-blown purulent keratoconjunctivitis developed in five of seven control animals vaccinated with placebo (71% attack rate) versus none of the eight guinea pigs immunized with two spaced intranasal doses of CVD 1205 (Noriega et al., 1996). No side effects were noted. Protection of guinea pigs against wild-type challenge. On day 28 after the first immunization, the 16 guinea pigs that had received CVD 1205 or placebo were challenged with 3 x 10^7 CFU of wild-type S. flexneri 2a strain 2457T in 10 ml of PBS (Noriega et al., 1996). S. flexneri 2a strain CVD 1207 VO_0000677 Recombinant vector vaccine Protective efficacy against shigellosis following rechallenge was 70% (Kotloff et al., 2000). Shigella flexneri strain CVD 1207 carries deletions of the plasmid gene virG (also known as icsA), which encodes a protein responsible for cell-to-cell spread of Shigella in the intestinal epithelium; (ii) the chromosomal gene set encoding Shigella enterotoxin 1 (ShET1), which is present almost exclusively in S. flexneri 2a; (iii) the plasmid gene sen, encoding Shigella enterotoxin 2 (ShET2), which is present in virtually all serotypes of Shigella; and (iv) the guaBA chromosomal operon that regulates synthesis of IMP dehydrogenase (encoded by guaB) and GMP synthetase (encoded by guaA), two enzymes employed in the distal de novo purine biosynthesis pathway. CVD 1207 thus expresses type-specific O-polysaccharide and invades epithelial cells (albeit less competently than the wild type) but undergoes only limited intracellular proliferation and intercellular spread and has no detectable enterotoxic activity (Kotloff et al., 2000). Recombinant protein preparation CVD 1207 was constructed from wild-type S. flexneri 2a strain 2457T by a series of double homologous recombinations using suicide plasmid deletion cassette technology as described in detail elsewhere. In brief, a specific, in-frame deletion mutation in the guaBA operon was first introduced, followed by a second in-frame deletion mutation in the plasmid virulence gene virG. The chromosomal mutation set was accomplished with deletion of 85% of subunit A of set. Finally, a sen cassette was constructed by fusing two 700-bp segments that include the N and C termini of sen minus 300 bp corresponding to the putative active site in the N-terminal region. The ars operon, conferring resistance to arsenite, was cloned into the sen locus to allow facile transfer of the double-deletion mutation (virG and sen) virulence plasmid to candidate Shigella vaccine strains and as a marker to distinguish CVD 1207 in the field. As previously described, CVD 1207 does not grow in minimum medium unless supplemented with guanine. The lack of enterotoxic activity has been confirmed in Ussing chambers. CVD 1207 is significantly less invasive for HeLa cells than its wild-type parent strain 2457T (approximately 1 log unit fewer intracellular CFU detected) but does not differ from its single-mutant strain progenitor guaBA CVD 1204 (unpublished observations). CVD 1207 undergoes fewer intracellular generations in HeLa cells than either CVD 204 (10-fold; 4.5 doublings in 4 h) or 2457T (30-fold; 5 doublings in 4 h) (unpublished observations) (Kotloff et al., 2000). A dose-related, immunoglobulin A antibody-secreting cell (ASC) response to S. flexneri 2a O-specific lipopolysaccharide was seen, with geometric mean peak values of 6.1 to 35.2 ASCs/10^6 peripheral blood mononuclear cells (PBMC) among recipients of 10^7 to 10^10 CFU. The cytokine response to Shigella-specific antigens observed in volunteers’ PBMC following vaccination suggested a Th1 pattern with stimulation of gamma interferon and absence of interleukin 4 (IL-4) or interleukin 5(Kotloff et al., 2000). Groups of 3 to 7 outpatient volunteers were assigned, in an incremental fashion, to receive a single oral dose of CVD 1207 at a desired inoculum (the actual inocula administered are in parentheses) of either 10^6,10^7, 10^8, 10^9, or 10^10 CFU. Fasting volunteers swallowed the vaccine suspended in a solution of NaHCO3 buffer, as previously described (Kotloff et al., 2000). Fecal excretion of the vaccine strain in the volunteer’s stools was measured on days 1, 2, 3, 7, 10, 14, and 21 after ingestion of the vaccine. The duration of excretion was 1 to 3 days except for two recipients of ca. 10^9 CFU, who each had one additional positive stool culture 2 weeks after vaccination (Kotloff et al., 2000). Some test subjects experienced diarrhea and vomiting. No subjects experienced fever or dysentery (Kotloff et al., 2000). S. flexneri Invaplex 50 Subunit Vaccine VO_0011468 Subunit vaccine Research Intranasally Isolated invasin complex (invaplex), which contains the major antigens of virulent Shigella, is shown to be immunogenic when delivered by a mucosal route without the need for any additional adjuvant. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. A novel method has been developed for isolating a macromolecular complex containing the major known virulence factors and immunogens from intact, viable, virulent shigellae. This structure was referred as the invasin complex, or invaplex. It has been possible to isolate two forms of the invaplex, called invaplex 24 and invaplex 50, by FPLC ion-exchange chromatography from S. flexneri 2a and S. flexneri 5. Both forms contain the invasins (IpaB, IpaC, and IpaD) and LPS, but IpaA and VirG, a truncated form of VirG, were found only in Invaplex 50. Other unidentified proteins were also present in both invaplex preparations (Turbyfill et al., 2000). Intranasally IpaB, IpaC, and IpaD, and LPS (Turbyfill et al., 2000). Recombinant protein preparation Recombinant protein preparation Recombinant protein preparation BALB/cByJ The ability of the invaplex fractions to promote an immune response in BALB/cByJ mice was tested in groups of five mice. Each mouse was immunized intranasally with 5 μg of invaplex 24 or invaplex 50 from S. flexneri 2a or S. flexneri 5 on days 0, 14, and 28. Saline was used to immunize control animals. A total antigen volume of 25 μl was delivered in 5 to 6 small drops applied to the external nares with a micropipette (Turbyfill et al., 2000). A significant level of protection against lethal challenge was achieved in mice immunized with S. flexneri 2a invaplex 50. Invaplex-immunized mice lost weight upon challenge, but by days 3 to 4 they began to recover and gain weight whereas control mice soon died. Similar levels of protection were afforded by invaplex 50 (10 of 15 mice survived) (Turbyfill et al., 2000). Three weeks after the final immunization with either S. flexneri 2a invaplex 24, invaplex 50, or saline, mice (15 per group) were challenged intranasally with a lethal dose of S. flexneri 2a 2457T (107 CFU/30 μl) as described for the mouse lung model (18). The mouse challenge dose was prepared from a frozen lot of S. flexneri 2a that had been harvested during the log phase of growth, which is the time of optimal invasiveness for shigellae, and then stored in liquid nitrogen (Turbyfill et al., 2000). S. flexneri strain Sfl 124 VO_0000673 Live, attenuated vaccine Homologous protection occurred after the initial infection with the virulent strain (Hartman et al., 1991). This vaccine is derived from S. flexneri strain SFl 114, which was constructed by making the virulent parent strain Sfl1 an aroD mutant. This rendered it dependent on aromatic metabolites not available in mamillian tissues. The tetracycline resistance properties of Sfl 114 were removed, and this resulting vacccine was called SFl 124 (Hartman et al., 1991). The vaccines were prepared in a lactose-phosphate-glutamate medium with dextran 10 added, then lypholized. All vaccines were rehydrated from the lypholized state with distilled water and diluted with phosphate-buffered saline. Each vaccine contained 3 x 10^8 to 5 x 10^8 organisms, and contained approximately 0.05 ml of cell suspension (Hartman et al., 1991). The antigen for this vaccine is Sfl 124, which is an S. flexneri Y strain. This strain was derived through the strain Sfl 114 (Hartman et al., 1991). Gene mutation Sera obtained from guinea pigs reacted with IpA proteins and showed no reaction to the pUC19 control (Hartman et al., 1991). Hartley Male Hartley guinea pigs were innoculated. Each guinea pig received 0.05 ml of cell suspension in the conjunctival sac of each eye with a dropper. Immunization occurred on days 0,1,14, and 15. Follwing vaccination, guinea pigs were evaluated daily for the development of keroconjunctivitis (Hartman et al., 1991). Not noted. The attack rate following previous infection was less than 20%. Protection was still more than 80% 7 weeks postinfection (Hartman et al., 1991). The only side effect was keroconjunctivitis (Hartman et al., 1991). Animals were challenged with the same strain 4, 7, or 13 weeks after infection (Hartman et al., 1991). S. sonnei strain WRSS1 VO_0000678 Recombinant vector vaccine WRSS1 vaccine is remarkably immunogenic in doses ranging from 10^3 to 10^6 CFU (Kotloff et al., 2002). WRSS1 is a stable S. sonnei mutant with a deletion in virG (Kotloff et al., 2002). The final composition of the vaccine consisted of 3.7 x 10^10 CFU of WRSS1 per vial in PBS containing 7.5% dextran T10, 2% sucrose, and 1.5% glycerol as a cryopreservative (Kotloff et al., 2002). Gene mutation WRSS1 was constructed from the Mosely strain of S. sonnei. A parent strain was selected that exhibited stability of the form I colonial phenotype, then sacB suicide vector pCVD422 was used to replace the wild-type virG allele with virG possessing a 212-bp deletion. In preclinical experiments (Kotloff et al., 2002). Vaccination elicited vigorous IgA ASC anti-LPS responses in all of the groups. ASC responses were less common and smaller in magnitude in the IgG anti-LPS assay and in both anti-Ipa assays. Geometric mean peak postvaccination anti-LPS serum IgG and fecal IgA titers were also robust. Most of the subjects exhibited a fourfold rise in serum and/or fecal anti-LPS antibody titers. Whereas the anti-LPS IgA ASC and fecal antibody responses tended to increase with the dose, a similar trend was not apparent in serum antibody responses. Postvaccination antigen-specific proliferative responses and increases in IL-10 production were not seen (Kotloff et al., 2002). Fasting volunteers ingested 2g of sodium bicarbonate buffer dissolved in 150 ml of water, followed 1 min later by 30 ml of water containing the assigned vaccine dose or no vaccine (placebo) (Kotloff et al., 2002). Side effects included fever, loose stools or aysmptomatic diarrhea, and mild cramps (Kotloff et al., 2002). This is a Phase I study. The protective efficacy and immunogenicity of WRSS1 were measured with the guinea pig keratoconjunctivitis model. Ocular immunization with 3 × 10^8 to 4 × 10^8 CFU of WRSS1/eye on days 0 and 14. In animals immunized with WRSS1 grown from overnight plate cultures, 13 of 16 eyes showed no signs of disease (83% complete protection), while 3 eyes showed mild conjunctivitis (17% partial protection). When reconstituted lyophilized cultures were used, 10 of 16 eyes did not develop disease (63% complete protection), while 4 eyes developed mild disease (25% partial protection). In both cases, protection against challenge was significant by the Fisher exact test (P < 0.001), and there was no significant difference in the levels of protection conferred by the two formulations. Four weeks after the last immunization, both the immunized animals and the unimmunized control animals were challenged with 4 × 10^8 CFU of virulent S. sonnei 53G/eye. WRSS1 was found to be both immunogenic and protective in the guinea pig keratoconjunctivitis model (Hartman and Venkatesan, 1998). WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgG responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002). WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgA responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002). SC602 VO_0000663 Live, attenuated vaccine Attenuated. The Shigella flexneri 2a SC602 vaccine candidate carries deletions of the plasmid-borne virulence gene icsA (mediating intra- and intercellular spread) and the chromosomal locus iuc (encoding aerobactin). The antigen for this vaccine is Shigella flexneri 2a strain SC602 (Coster et al., 1999). Recombinant protein preparation This SC602 vaccine was constructed with S. flexneri 2a strain 454 as the progenitor. The iuc mutation neccessary for producing SC602 was generated by recombination of iuc::Tn10 into the chromosome by using phage P1 transduction. Spontaneous excision of the tetracycline resistance gene, and its flanking regions including the iuc locus, was selected by growth on fusaric acid medium. The icsA gene was inactivated by double recombination with a kanamycin resistance-sucrose sensitivity cartridge carrying flanking regions of icsA. Deletion of the Kmr-sacB cartridge was selected by growth on sucrose, and the resistant clones were screened for retention of the invasive phenotype in HeLa cells. An isolate designated SC602 had suffered a deletion of the entire icsA gene along with substantial flanking sequences.This SC602 isolate was expanded into a master cell bank and was used in the vaccines (Coster et al., 1999). Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS. Other correlates of protection against all symptoms included urinary sIgA responses against 2a LPS in addition to IgG ASC and IgG serum responses. ASC levels peaked on day 7 and ELISA titers peaked on day 14 for vaccination(Coster et al., 1999). Volunteers fasted for 90 minutes before and after vaccination. The inoculum was ingested by each volunteer 2 min after ingestion of 120 ml of the sodium bicarbonate solution. Placebo controls received sodium bicarbonate buffer with no added bacteria. SC602 dose selection studies. Thirty-three subjects were enrolled in the initial, placebo-controlled dose selection trial: eighteen subjects received the SC602 vaccine and fifteen received sodium bicarbonate placebo (Coster et al., 1999). Robust and prolonged intestinal colonization by S. flexneri 2a was observed in all volunteers who had ingested the SC602 vaccine. The peak excretion of vaccine was 10^4 to 10^6 CFU/g of stool regardless of the dose ingested (Coster et al., 1999). SC602 gave significant protection against fever and severe shigellosis (Coster et al., 1999). Reportable intestinal symptoms included abdominal cramps, nausea, emesis, tenesmus, and gas. Constitutional symptoms in- cluded headache, myalgia, arthralgia, loss of appetite, and fatigue (Coster et al., 1999). The challenge inoculum, containing approximately 10^3 CFU of virulent S. flexneri 2a strain 2457T, was prepared and administered with sodium bicarbonate as described previously. All subjects who were vaccinated or challenged with S. flexneri were treated with ciprofloxacin (Coster et al., 1999). Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS as compared to titers on day 0. Four of 12 vaccinees experienced a significant increase in IgA titers (Coster et al., 1999). Correlates of protection against all symptoms included IgG ASC and IgG serum responses. A majority of volunteers had IgG anti-Ipa responses. Antibody titers were compared to day 0 titers (Coster et al., 1999). Shigella flexneri aroD mutant vaccine VO_0002923 Live, attenuated vaccine Research Oral immunization Oral immunization Gene mutation This aroD mutant is from Shigella flexneri (Kärnell et al., 1993). An aroD mutant is highly attenuated in monkeys (Kärnell et al., 1993). An aroD mutant induces significant protection in monkeys from challenge with wild type S. flexneri (Kärnell et al., 1993). Shigella flexneri envZ mutant vaccine SC433 VO_0002924 Live, attenuated vaccine Research Intragastric immunization Intragastric immunization Gene mutation This envZ mutant is from Shigella flexneri (Sansonetti et al., 1991). An envZ mutant (SC433) is greatly decreased in virulence in macaque monkeys, though some mild clinical signs were still recorded (Sansonetti et al., 1991). An envZ mutant is highly protective in macaque monkeys against a challenge of wild type S. flexneri delivered 1 month after inoculation (Sansonetti et al., 1991). Shigella ribosome-based Vaccine (SRB) VO_0000739 Live, attenuated vaccine The ribosome acted as the adjuvant in the vaccine, carrying the O-antigen and other cell-wall antigens (Shim et al., 2007). SRV is immunogenic and provides protective efficacy in mice (Shim et al., 2007). Virulent S. flexneri 2a 2457T strains were incubated, then cultured. The cells were then subjected to a high-pressure homogenizer to break down the bacterial ribosome. The ribosome was then purfied. The O-antigen concentration accounted for approximately 5% of the preparation. This vaccine is composed of O-antigen and ribosome isolated from S. flexneri 2a (Shim et al., 2007). The protective antigen for this vaccine is O-antigen from S. flexneri 2a (Shim et al., 2007). Both subcutaneous and intranasal vaccination induced high levels of Ag-specific IgG Ab in sera. Intranasal vaccination elicited robust levels of LPS-specific IgA Ab in the mucosal secretions. The heightened levels were identical to those produced by vaccination with the S. flexneri 2a SC602 strain (Shim et al., 2007). BALB/c Mice were subcutaneously or intranasally vaccinated on days 0 and 14 with a 2.5 microgram dose of the O-antigen. For a control, attenuated S. flexneri 2a SC602 strain (5 x 10^6 CFU) was administered (Shim et al., 2007). Groups of mice vaccinated intranasally with SRV demonstrated less severe pneumonia than those mice that received subcutaneous vaccines. SRV administration via the parenteral route did not effictively protect against the challenge. Almost 65% of mice that received the intranasal vaccine survived the two vaccine doses compared to about 20% of mice that received the subcutaneous dose. These data suggest that a higher degree of protective immunity is conferred against Shigella by SRV when it is administered by the intranasal route (Shim et al., 2007). One week after the second vaccination, the mice were challenged with virulent S. flexneri 2a (1 x 10^7 or 5 x 10^7 CFU) to induce pulmonary pneumonia (Shim et al., 2007). Shigella sonnei virG/senA/senB mutant vaccine WRSs2 VO_0002928 Live, attenuated vaccine Research Oral immunization Oral immunization Gene mutation This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010). Gene mutation This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010). Gene mutation This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010). A virG, senA, and senB mutant is attenuated in guinea pigs (Barnoy et al., 2010). A virG, senA, and senB mutant induces significant protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010). Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010). Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010). Shigella sonnei virG/senA/senB/msbB2 mutant vaccine WRSs3 VO_0002927 Live, attenuated vaccine Research Oral immunization Oral immunization Gene mutation This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010). Gene mutation This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010). Gene mutation This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010). Gene mutation This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010). A virG, senA, senB, and msbB2 mutant is attenuated in guinea pigs (Barnoy et al., 2010). A virG, senA, senB, and msbB2 mutant induces protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010). Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010). Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010). Ty21a-O-Ps (Shigella dysenteriae ) VO_0004703 Recombinant vector vaccine Research Intramuscular injection (i.m.) A tandemly-linked rfb-rfp gene cassette was cloned into low copy plasmid pGB2 to create pSd1 (Xu et al., 2007). Intramuscular injection (i.m.) Groups of 10 mice were inoculated intraperitoneally with one or two 0.5 ml doses of either vaccine suspension or sterile PBS (Xu et al., 2007). VO_0003057 Animal immunization studies showed that Ty21a (pSd1) induces protective immunity against high stringency challenge with virulent S. dysenteriae 1 strain 1617 (Xu et al., 2007). Immunized and control mice were challenged 5 weeks after immunization with a lethal dose of 7.5 × 10^5 cfu of the freshly grown, mid-log phase virulent S. dysenteriae 1 stxA-deleted strain (1617Δ stxA) in 0.5 ml of 5% hog gastric mucin (Sigma) in sterile PBS (Xu et al., 2007). Typhi strain Ty21a-LPS-Shigella VO_0004701 Recombinant vector vaccine Research Intramuscular injection (i.m.) Ty21a-Ss simultaneously expresses both homologous Ty21a and heterologous S. sonnei O-antigens (Dharmasena et al., 2013). Intramuscular injection (i.m.) Mice were immunized with vaccine candidate strains (Ty21a-Ss) or negative controls Ty21a alone and PBS (Dharmasena et al., 2013). VO_0003057 Ty21a-Ss elicited strong dual anti-LPS serum immune responses and 100% protection in mice against a virulent S. sonnei challenge (Dharmasena et al., 2013). Immunized and control mice were challenged intraperitoneally, 2 weeks after final immunization, with ∼5 × 10^6 CFU/ml of freshly grown, mid-log-phase virulent S. sonnei strain 53GI in 0.25 ml (∼2 × 10^6 CFU per mouse) of 5% hog gastric mucin (Sigma) dissolved in sterile saline (i.e. approximately 100 times the 50% lethal infectious dose [LD50]) (Dharmasena et al., 2013). AroA Shigella flexneri 2a str. 2457T 1077373 30062442 S0967 NC_004741.1 NP_836613.1 620 945133 946416 + 3-phosphoshikimate 1-carboxyvinyltransferase 5.14 46167.3 427 catalyzes the formation of 5-O-(1-carboxyvinyl)-3-phosphoshikimate from phosphoenolpyruvate and 3-phosphoshikimate in tryptophan biosynthesis >GeneID|1077373 [Shigella flexneri 2a str. 2457T ] 945133..946416 tacaacccatcgctcgtgtcgatggcactattaatctgcccggttccaagagcgtttctaaccgcgcttt attgcttgcggcattagcacacggcaaaacagtattaaccaatctgctggatagcgacgacgtgcgccat atgctgaatgcattaacagcgttagggttaagctatacgctttcagccgatcgtacgcgttgcgaaatta tcggtaacggcggtccattacacgcagaaggtgccctggagttgttcctcggtaacgccggaacggcaat gcgtccgctggcggcagctctttgtctggatagcaatgatattgtgctgaccggtgagccgcgtatgaaa gagcgcccgattggtcatctggtggatgcgctgcgcctgggcggggcgaagatcacttacctggaacaag aaaattatccgccgttgcgtttacagggcggctttactggcggcaacgttgacgttgatggctccgtttc cagccaattcctcaccgcactgttaatgactgcgcctcttgcgccggaagatacggtgattcgtattaaa ggcgatctggtttctaaaccttatatcgacatcacactcaatctgatgaagacgtttggtgttgaaattg aaaatcagcactatcaacaatttgtcgtaaaaggcgggcagtcttatcagtctccgggtacttatttggt cgaaggcgatgcatcttcggcttcttacttcctggcagcagcagcaatcaaaggcggcactgtaaaagtg accggtattggacgtaacagtatgcagggtgatattcgctttgctgatgtgctggaaaaaatgggcgcga ccatttgctggggcgatgattatatttcctgcacgcgtggtgaactgaacgctattgatatggatatgaa ccatattcctgatgcggcgatgaccattgccacggcggcgttatttgcaaaaggcaccaccacgctgcgc aatatctataactggcgtgttaaagagaccgatcgcctgtttgcgatggcaacagaactgcgtaaagtcg gcgcggaagtggaagaggggcacgattacattcgtatcactcctccggaaaaactgaactttgccgagat cgcgacatacaatgatcaccggatggcgatgtgtttctcgctggtggcgttgtcagatacaccagtgacg attcttgatcccaaatgcacggccaaaacatttccggattatttcgagcagctggcgcggattagccagg cagcctgaatgaacaacgggcaat >gi|30062442|ref|NP_836613.1| 3-phosphoshikimate 1-carboxyvinyltransferase [Shigella flexneri 2a str. 2457T ] MESLTLQPIARVDGTINLPGSKSVSNRALLLAALAHGKTVLTNLLDSDDVRHMLNALTALGLSYTLSADR TRCEIIGNGGPLHAEGALELFLGNAGTAMRPLAAALCLDSNDIVLTGEPRMKERPIGHLVDALRLGGAKI TYLEQENYPPLRLQGGFTGGNVDVDGSVSSQFLTALLMTAPLAPEDTVIRIKGDLVSKPYIDITLNLMKT FGVEIENQHYQQFVVKGGQSYQSPGTYLVEGDASSASYFLAAAAIKGGTVKVTGIGRNSMQGDIRFADVL EKMGATICWGDDYISCTRGELNAIDMDMNHIPDAAMTIATAALFAKGTTTLRNIYNWRVKETDRLFAMAT ELRKVGAEVEEGHDYIRITPPEKLNFAEIATYNDHRMAMCFSLVALSDTPVTILDPKCTAKTFPDYFEQL ARISQAA Virmugen An aroA and virG mutant (CVD 1203) is attenuated in guinea pigs, as shown by the Sereny test. Guinea pigs inoculated with CVD 1203 were also protected from challenge with wild type S. flexneri [Ref653:Noriega et al., 1994]. AroD Shigella flexneri 2a str. 2457T 1078189 30063207 S1855 NC_004741.1 NP_837378.1 620 1794511 1795269 + 3-dehydroquinate dehydratase 5.17 27517.5 252 catalyzes the dehydration of 3-dehydroquinate to form 3-dehydroshikimate in aromatic amino acid biosynthesis >GeneID|1078189 [Shigella flexneri 2a str. 2457T ] 1794511..1795269 tcgtcattggtgcgggcgcacctaaaatcatcgtctcgctgatggcgaaagatatcgcccgcgtgaaatc cgaagctctcgcctatcgtgaagcggactttgatattctggaatggcgtgtggaccactttgccgacctc tccaatgtggagtctgtcatggcggcggcaaaaattctccgtgaaaccatgccagaaaaaccgctgctgt ttaccttccgcagtgccaaagaaggcggcgagcaggcgatttccaccgaggcttatattgctctcaatcg tgcagccatcgacagcggcctggttgatatgatcgatctggagttatttaccggcgatgatcaggtcaaa gaaaccgtcgcctacgcccacgcgcatgatgtgaaagttgtcatgtccaaccatgacttccataaaacgc cggaagccgaagaaatcattgcccgtctgcgcaaaatgcagtccttcgacgccgatattcctaagattgc gctgatgccgcaaagtaccagcgatgtgctgacgttgcttgccgcgaccctggagatgcaggagcagtat gccgatcgtccaatcatcacgatgtcgatggcaaaaactggcgtaatttctcgtctggttggtgaagtat ttggctcggcggcaacttttggtgcggtaaaaaaagcctctgcgccagggcaaatctcggtaaatgattt gcgcacggtattaactattttacatcaggcataagcaataatatttcggcggaaatacc >gi|30063207|ref|NP_837378.1| 3-dehydroquinate dehydratase [Shigella flexneri 2a str. 2457T ] MKTVTVKDLVIGAGAPKIIVSLMAKDIARVKSEALAYREADFDILEWRVDHFADLSNVESVMAAAKILRE TMPEKPLLFTFRSAKEGGEQAISTEAYIALNRAAIDSGLVDMIDLELFTGDDQVKETVAYAHAHDVKVVM SNHDFHKTPEAEEIIARLRKMQSFDADIPKIALMPQSTSDVLTLLAATLEMQEQYADRPIITMSMAKTGV ISRLVGEVFGSAATFGAVKKASAPGQISVNDLRTVLTILHQA Virmugen An aroD mutant is highly attenuated in monkeys and induces significant protection from challenge with wild type S. flexneri [Ref1675:Kärnell et al., 1993]. envZ Shigella flexneri 5 str. 8401 4207729 110807236 SFV_3409 CP000266 YP_690756 2LFR 373384 3465716 3467068 - osmolarity sensor protein 6.81 46960.53 450 Also known as ompBmembrane-localized osmosensor; histidine kinase; in high osmolarity EnvZ autophosphorylates itself and transfers phosphoryl group to OmpR >gi|110804074:3465716-3467068 Shigella flexneri 5 str. 8401 chromosome, complete genome TTTACCCTTCTTTTGTCGTGCCCTGCGCCCGCGTTACCGGCACTGGCAGCCAGGCGCGAATGGAAAGCCC GCCCCGCTCGCTGGTGCCAAGCTCCAGCATCCCGTTATGGTTATCCACGATACGCTGCACAATTGCCAGC CCTAATCCCGTGCCGCTAATGGTGCGCGCACTGTCGCCGCGGACAAACGGCTGGAACAGGTGCTTACGTT GTTCCGGCGCAATTCCCGGACCGTCATCTTCCACCTGGAACCAGGCGCGATTCGGCTCCGTTCCGCTGCT GACTTTGATCCAGCCATTGCCATAACGGGCGGCGTTGACCACCATATTCGCCACCGCGCGTTTGATCGAC AGCGGGTGCATTTTCACTTCAATGCTGCCGGGGTAAAGCGCGGTTTCAATTTCCCGCTCATAGCCACTTT CGGCAGCAATCACCTCACCGAGCACTGCATTAAGATCCGCCATTTCCATCGGCATCTCCTGCCCGGTGCG CAGGTAGTCGATAAACTGCTCAATGATGGCGTTGCACTCTTCGATATCTTTATTGATCGATTCTGCCAGA TAGCCATCCTGCTCGCTCATCATCTCAGTCGCCAGGCGAATACGCGTCAGCGGCGTGCGCAAGTCGTGAC TTACCCCCGCCATCAGCAGCGTGCGGTCATCCGCCAGTTGCTTAACACCAGCCGCCATATGGTTAAAGGC ACGGGTAACGGAACGCACCTCCGAAGCGCCATATTCACGCAGCGGCGGCGGAATAATCCCTTTACCAACC TGCAAGGCTGCGTGTTCGAGATCGACCAACGGTCGGTTCTGGATACGAATAAACAGCCACGCCCCGCCTA TCGCCAATAGCATAATCGCCAGCGTATAGCGGAACAGCGGAGAGAAATCGCCCTGATGAATTTCGGTCAG CGGCACGCGTACCCAGATATTGGGCGACAGCCAGGTTTTCAGCCAGACGACAGGCGAACTTTTGTTGACC TCAACGCGCACTTCCGTCGGGCCGCCCAGTTGCTGTGCCATCTGATGGCTTAAGAATTCATAGTGTTGCG CCCAACGCAGACCTGCCTCTTCGGCAGCCTCGTTGGAGTAGAGAGAGATCCCCAGCTCACGGTAGATCTC CCGACGGAAAGCGGGAGGCACAACCAACTGCGTGCCGTCCTCCAGTTGCAGTTTGTCGGTCATCAACATA CGCACTTCGTACGCGAGGACTTTATTAAACTGCTGGAGGCTCGGCAAAATCGCGAAGTTCAGCACCACCA GATAAGTCGTCACCAGGCTGGCGAACAGCAAGGTGACGATGAGCAATAACGTACGGGCAAATGAACTTCG TGGCGAGAAGCGCAATCGCCTCA >gi|110807236|ref|YP_690756.1| osmolarity sensor protein [Shigella flexneri 5 str. 8401] MRRLRFSPRSSFARTLLLIVTLLFASLVTTYLVVLNFAILPSLQQFNKVLAYEVRMLMTDKLQLEDGTQL VVPPAFRREIYRELGISLYSNEAAEEAGLRWAQHYEFLSHQMAQQLGGPTEVRVEVNKSSPVVWLKTWLS PNIWVRVPLTEIHQGDFSPLFRYTLAIMLLAIGGAWLFIRIQNRPLVDLEHAALQVGKGIIPPPLREYGA SEVRSVTRAFNHMAAGVKQLADDRTLLMAGVSHDLRTPLTRIRLATEMMSEQDGYLAESINKDIEECNAI IEQFIDYLRTGQEMPMEMADLNAVLGEVIAAESGYEREIETALYPGSIEVKMHPLSIKRAVANMVVNAAR YGNGWIKVSSGTEPNRAWFQVEDDGPGIAPEQRKHLFQPFVRGDSARTISGTGLGLAIVQRIVDNHNGML ELGTSERGGLSIRAWLPVPVTRAQGTTKEG Virmugen An envZ mutant (SC433) is greatly decreased in virulence in macaque monkeys, though some mild clinical signs were still recorded. This mutant is also highly protective against a challenge of wild type S. flexneri delivered 1 month after inoculation [Ref2051:Sansonetti et al., 1991]. GuaB Shigella flexneri 5 str. 8401 4207514 110806439 SFV_2555 CP000266 YP_689959 373384 2617798 2619270 - inosine 5'-monophosphate dehydrogenase 6.37 47489.31 490 catalyzes the synthesis of xanthosine monophosphate by the NAD+ dependent oxidation of inosine monophosphate >NC_008258.1:2617798-2619270 Shigella flexneri 5 str. 8401, complete genome ATCAGGAGCCCAGACGGTAGTTCGGGGACTCTTTAGTAATGGTCACGTCGTGAACGTGGCTTTCCTGAAT GCCCGCACCGCTGATACGTACAAACTCCGCTTTAGTACGCAGTTCGTCGATAGTACCACAGCCGGTCAGA CCCATACAGGAGCGCAGGCCGCCCATCTGCTGGTGAATGATCTCTTTCAGGCGACCTTTATAAGCTACGC GACCTTCGATACCTTCCGGCACCAGTTTGTCGGCAGCGTTATCGCTCTGGAAATAACGGTCAGAGGAACC TTTGGACATCGCGCCCAGGGAACCCATACCACGGTAAGATTTATAAGAACGGCCCTGGTAGAGTTCGATT TCACCCGGAGATTCTTCAGTACCCGCCAGCATGGAACCTACCATCACCGCGCTTGCGCCAGCGGCGATAG CTTTGGCGATGTCGCCGGAGAAGCGAATACCACCATCTGCGATAACCGGAATACCGGTGCCTTCCAGGGC TTCAACTGCGTCAGCAACGGCAGTGATCTGCGGAACACCTACGCCAGTAACGATACGAGTCGTACAGATA GAACCAGGGCCGATACCGACTTTAACCGCGCTGCAACCAGCTTCTGCCAAAGCGCGTGCACCTGCAGCTG TTGCCACGTTGCCGCCGATGATTTGCAGATCCGGATATTTAGCACGGGTTTCACGGATACGCTGCAAAAC GCCTTCTGAGTGACCGTGGGAGGAGTCGATCAGCAGAACGTCAACGCCAGCGGCAACCAGCGCGTCAACA CGCTCTTCGTTACCCGCACCTGCGCCAACTGCAGCACCAACACGCAGACGGCCTTGCTCGTCTTTACAGG CGTTCGGTTTACGTTCCGCTTTCTGGAAGTCTTTCACGGTGATCATGCCGATCAGGTGGAATTCGTCATC AACCACCAGCGCTTTTTCAACGCGTTTTTCGTGCATTTTTGCCAGCACCACTTCACGGGCTTCACCTTCA CGCACGGTGACCAGACGCTCTTTCGGCGTCATGTAAACGCTAACCGGCTGGTTCAGGTCGGTAACAAAAC GCACGTCACGACCGGTGATAATACCCACCAGTTCGTTTTCTTCGGTAACGACCGGATAGCCCGCAAAACC GTTACGCTCGGTCAGTTCTTTCACTTCGCGCAGCGTCGTGGTTGGCAGAACAGTCTGCGGATCAGTCACC ACACCAGATTCGTGTTTTTTCACACGGCGAACTTCTTCTGCCTGGCGTTCAATGGACATGTTTTTGTGGA TAAAGCCGATACCGCCTTCCTGAGCCAGAGCAATAGCCAGGCGCGCTTCCGTTACGGTATCCATTGCTGC GGAAAGCATAGGGATATTCAGACGAATAGTTTTCGTCAGCTGGGTGCTGAGGTCAGCAGTATTCGGCAGA ACGGTAGAATGAGCAGGAACGAGGAGAACGTCGTCAAACGTCAGAGCTTCTTTAGCGATACGTAGCATGG GCA >YP_689959.1 inosine 5'-monophosphate dehydrogenase [Shigella flexneri 5 str. 8401] MPMLRIAKEALTFDDVLLVPAHSTVLPNTADLSTQLTKTIRLNIPMLSAAMDTVTEARLAIALAQEGGIG FIHKNMSIERQAEEVRRVKKHESGVVTDPQTVLPTTTLREVKELTERNGFAGYPVVTEENELVGIITGRD VRFVTDLNQPVSVYMTPKERLVTVREGEAREVVLAKMHEKRVEKALVVDDEFHLIGMITVKDFQKAERKP NACKDEQGRLRVGAAVGAGAGNEERVDALVAAGVDVLLIDSSHGHSEGVLQRIRETRAKYPDLQIIGGNV ATAAGARALAEAGCSAVKVGIGPGSICTTRIVTGVGVPQITAVADAVEALEGTGIPVIADGGIRFSGDIA KAIAAGASAVMVGSMLAGTEESPGEIELYQGRSYKSYRGMGSLGAMSKGSSDRYFQSDNAADKLVPEGIE GRVAYKGRLKEIIHQQMGGLRSCMGLTGCGTIDELRTKAEFVRISGAGIQESHVHDVTITKESPNYRLGS Protective antigen human IgA Homo sapiens 2632187 CDD:209398 CDD:197704 9606 ? IgA 131 Immunoglobulin domain; cl11960 >gi|2632187|emb|CAA10818.1| IgA [Homo sapiens] LQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDT SKNQFSLKLSSVTAADTAVYYCASRVGYCSSTSCYTFDYWGQGTLVTVSSASPTSPKVFPL Vaximmutor Vaximmutor IcsA/VirG Shigella flexneri 2a str. 301 1238021 31983529 CP0182 NC_004851.1 NP_858315.1 3ML3 pCP301 149644 152952 + IcsA (VirG), outermembrane protein exposed to the bacterial surface by a C-terminal autotransporter domain and involved in the movement of intracellular bacteria by binding to N-WASP 5.31 116243.6 1102 >GeneID|1238021 [Shigella flexneri 2a str. 301 ] 149644..152952 tcaccagacgctgcagttcagcattacgttcaacttcagctcgcaaggccaacaggtcataagccgcacg gaacttaggatgctccagcagtttccatgcgcgtttaccctgacgacgggacatacgcaactgcaactgc cagatatcgcgggttaacgtcgtcagacgtttcgggattgccagtgaacggcaggcttcgtccagcacgt cgttcatcgccagcgcgaaagcgtcgtgataggtcaggccgctttcctgggcgatcttctgtgccgtctc cagcagtgggtaccagaacatggcggcaaacaagaacgccgggttcacgcgcatatcgttatggatacgc gtatcggtattcttcagcacctgttcaatgatccgctccatcgggctgtcgccattttccgtgaagtagc gggtaatggtcgggaacagcggctggaacagatgatattcacacaacagcttataggtttcgtaaccgta gcccgcttgtagcagtttaagcgattcttcaaacaggcgtgccggtgggatatcgttcagcagggtagcg aggcgagggatcggttctgcggtttccgggctgatgcgcatacccaatttggcggcaaaacgtaccgcgc gcagcatacgtaccggatcttcacggtagcgcgtttccgggttaccaatcagacggataacgccgtcctt cagatccttcataccaccaacgtaatcacggacggtaaaatccgctacgctgtaatacaggctgttgata gtgaaatcgcggcgctgggcgtcttcttcgatggagccgaaaatgttgtcgcgcagcaacatgccgtttt gcccgcgttgggaggtcgtgcggtcgctgacgttaccttcgtggtgtccacggaaggtcgcaacttcgat aatctccgggccaaacattacatgagccagacggaaacggcgacccaccaggcggcagttacggaacagt ttgcgcacctgctcaggcgtggcgttagtggttacgtcaaaatctttcggctttttgccaagtaacaggt cgcgcacgccgccgccaaccagccaggcttcgtatcccgctttgttgagcctgtacattaccttcagggc attttcactgatatctttgcgggaaatagcatgctgctcacgcgggatcaccgtcacctgtggacgggcg actgcctgttcagcctcgctttcctcgcggcttagcaccttgcggcaaaaattagcgactcgggtaaaaa tagtacacctcggtagtgtcaaacatcattcaggacaaaaaaatagcggctaatcatagctcagcatgac gcatttgagaatgttgaatttacaattgccgactcgggcacggcggtcagcatccagtttttgacggctg actgaaggatttgctcgacgctgaaatcctgccagtgtgcttctgcctgctgccccagaaattgaagtgc cgcgattagtaccgggcgtggatcgcctttcggcaacgcaggcgcatgattctgcttggaaagtttagcg ccttgtggattaagcgccagcggcagatgaatgtaatctggcactttccagccaaaaagctggtacagcg ggatttgccttactgttggttcaatcagatcagccccacgcactatttctgtaacgccctggaaatgatc atcaaccacaacagccaggttgtaggcgaacaacccatcacggcgatgaatgataaaatcttcccgtgcc agtttttcgtcggcgtgaataatgcctcgcagcaggtcagtaaattgcgtgaccggatgctgctggcgga tacgcactgcggcgttgtctggtccatgatgcaacacccggcaatgaccgtcgtaaataccgccaatgct ttgaatacgcgcacgcgtacaggtgcagtaataacttagtccttgttcatgtaaccaggcgagtgcttca cgataggcgtcgtgacgttgcgattgccagagaacatcgccgtcccagtgcagaccgtaatgttccagct ggcgcaggatagtttctgcggcaccgggaacttcacgaggcgggtcgatatcttctatgcgtaccagcca gcgaccttgccgggcgcgagcctgcaaatagctgccgagcgcggcgatcagagagccaaaatgaagctcg ccggaaggagagggggcgaagcggccaatatactgtgtgtctgtcatctctttgaacaaaaaataaggcg ggagcatttcccgcctgtggtaaacgtgatggaacggctgtaattagccagccatctgtttttcgcgaat ttcagccagcgttttgcagtcgatgcacagatcggctgtcgggcgcgcttccagacggcgaataccaatt tcaacaccgcaggattcgcagtagccgaaatcttcgtcttccacttttttcagcgtcttctcgatctttt tgatcagcttacgctcgcgatcgcggttacgcagttcgaggctgaactcttcttcctgggctgcacggtc taccgggtccgggaagttggctgcttcatcctgcatatgtgtaacggtgcgatcgacttcatccctgagt tgattacgccatgcttccagaatacgacggaagtgcgccagctgggcttcattcatatactcttcgcccg gcttctcctgatatggttccaccccagcgatggcgagaatactcagggacgatgttttacggttttgccc ttcttgcatgttgcttctccttaacacgcactatcgatccccatgttcgggggaaaaatgaggccgctat aaatagcagatgcttttccggatagcaattatctaaacgtaacacttgacaactgtgtgaggaaaagcgt atttgcgcacgcgaccagaatgtaaattaaccagttacttactttactacaatgtaaccggcagtgattt tttaagagccatgccttcagcagaaatttccgctttgtaagccagaatttctacccccctctgttgagct tctgacaatagttgcgcgtatttctcatcgatgtggcgcgcgggtgaaaaccgtgtaatggctgaatgca gcacggcgaaaaaaataaccgcacgctggccttcagccgctacgctcatcaactcccgaaggtgtttctg acctcgttcagtgaccgcatcgggaaaatatccctgttcgttctccgctaacgtaaccgatttcacttca atatagcagtctggacgcgaatccgcctgcaacataaagtcaatacggctgcgttcggagccgtatttta cttcgcttttcagcgagct >gi|31983529|ref|NP_858315.1| IcsA (VirG), outermembrane protein exposed to the bacterial surface by a C-terminal autotransporter domain and involved in the movement of intracellular bacteria by binding to N-WASP [Shigella flexneri 2a str. 301 ] MNQIHKFFCNMTQCSQGGAGELPTVKEKTCKLSFSPFVVGASLLLGGPIAFATPLSGTQELHFSEDNYEK LLTPVDGLSPLGAGEDGMDAWYITSSNPSHASRTKLRINSDIMISAGHGGAGDNNDGNSCGGNGGDSITG SDLSIINQGMILGGSGGSGADHNGDGGEAVTGDNLFIINGEIISGGHGGDSYSDSDGGNGGDAVTGVNLP IINKGTISGGNGGNNYGEGDGGNGGDAITGSSLSVINKGTFAGGNGGAAYGYGYDGYGGNAITGDNLSVI NNGAILGGNGGHWGDAINGSNMTIANSGYIISGKEDDGTQNVAGNAIHITGGNNSLILHEGSVITGDVQV NNSSILKIINNDYTGTTPTIEGDLCAGDCTTVSLSGNKFTVSGDVSFGENSSLNLAGISSLEASGNMSFG NNVKVEAIINNWAQKDYKLLSADKGITGFSVSNISIINPLLTTGAIDYTKSYISDQNKLIYGLSWNDTDG DSHGEFNLKENAELTVSTILADNLSHHNINSWDGKSLTKSGEGTLILAEKNTYSGFTNINAGILKMGTVE AMTRTAGVIVNKGATLNFSGMNQTVNTLLNSGTVLINNINAPFLPDPVIVTGNMTLEKNGHVILNNSSSN VGQTYVQKGNWHGKGGILSLGAVLGNDNSKTDRLEIAGHASGITYVAVTNEGGSGDKTLEGVQIISTDSS DKNAFIQKGRIVAGSYDYRLKQGTVSGLNTNKWYLTSQMDNQESKQMSNQESTQMSSRRASSQLVSSLNL GEGSIHTWRPEAGSYIANLIAMNTMFSPSLYDRHGSTIVDPTTGQLSETTMWIRTVGGHNEHNLADRQLK TTANRMVYQIGGDILKTNFTDHDGLHVGIMGAYGYQDSKTHNKYTSYSSRGTVSGYTAGLYSSWFQDEKE RTGLYMDAWLQYSWFNNTVKGDGLTGEKYSSKGITGALEAGYIYPTIRWTAHNNIDNALYLNPQVQITRH GVKANDYIEHNGTMVTSSGGNNIQAKLGLRTSLISQSCIDKETLRKFEPFLEVNWKWSSKQYGVIMNGMS NHQIGNRNVIELKTGVGGRLADNLSIWGNVSQQLGNNSYRDTQGILGVKYTF Virmugen An aroA and virG mutant (CVD 1203) is attenuated in guinea pigs, as shown by the Sereny test. Guinea pigs inoculated with CVD 1203 were also protected from challenge with wild type S. flexneri [Ref653:Noriega et al., 1994]. IgA Cavia porcellus IgG Homo sapiens 185362 CDD:143182 CDD:197704 CDD:143186 CDD:209398 9606 ? IgG 476 putative >gi|185362|gb|AAA02914.1| IgG [Homo sapiens] MDWTWRFLFVVAAATGVQSQMQVVQSGAEVKKPGSSVTVSCKASGGTFSNYAISWVRQAPGQGLEWMGGI IPLFGTPTYSQNFQGRVTITADKSTSTAHMELISLRSEDTAVYYCATDRYRQANFDRARVGWFDPWGQGT LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Vaximmutor IgG Fc receptor II Cavia porcellus 100192391 290543543 NP_001166520 10141 Un 11272753 11287230 + Fc-gamma-1/gamma-2 receptor 6.44 34213.92 341 Also known as FCGR2; FcRII >gi|347623371:11272753-11287230 Cavia porcellus strain inbred line 2N unplaced genomic scaffold, Cavpor3.0 supercont2_56, whole genome shotgun sequence ATTTGGTTGTTTTCTGGGTGGAGAGAAGCTGCATACTGTAGGAGTCAGCTTGCTGCAGAAGTGATGGCGA TCCCTTCGTTCTTACCTGTCCTTGGCACCAAGAGTCACCGAGCTGACTATAAGCCCTTGCAGACTTTGAG CCACATGCTGCTGTGGATAACTGTGCTATTCCTGGGTGAGTTGAGGGCCTGAGTAGGGAGGCAGGAGCAG GAATACCTGGGTTGAGGCTGATCTTGGGCAGGGATAAGGGTGGCCTAAGAAGCGTGTTGGAAAAATTAGG AGTATGGAGGCTGCGTGTTGCAGGTCTGACAACCTACTGGCTTTAGTTAGTAAAGCAAAGTTGGAGGAGT GGTTTCTTAACTTACTCGGTTTTAATGAGCACATAGTCTCTGATCCTCTGCCACTGCGTGTATCAGAACC TGCTCTGGGGGAAGTTTAATGATTCAACTTAAGTGACAAATGTGTGGCCAAACTATTTCCCTTTGACTCT ATTTCACATGAAACCACATCTTAGGCAAGAGAGGCAGTGCTGCTTTAGACAAGGCATGGAGAGGAGCTCT AAGATGCATTCTGGGGAGAAGAGCAATTGCTCCTCTCTGTGCTGCTGAAGCCACTTCATGTAGCAGAAGC CGGTTCTTTTTGCCCATAAAGAAATTTCCCTGAGAGGAACCACAGGGAACCGGGGCAAGGAGGACCCAAA AACATGGGCAGTTTTGGAATTGTCATTTATGGGACCAGAGAAATCATACATGCTTCCTTTCACTGCAGAA AGCATGGGCTGGGTCCTGGCACTGATCAGTGAGAAGGTCATTGTTTTAAGCCAAGATAGAGGAGTCTTTT CTGATCAGGATCTTTGCTATGAGCAGGGGACAGAAATTAATAGTGCTGTATATTTGAAAGAGGCTGTAGG GAGACCTGCAGGCAAGATTTTCCTCCAGTTGTGTTCCTGGGGGTTCCACTGTCACCTCTCACAGGAAGAC ACAACAGTCACTCTCCAAGTCACTTGCCCTAACTGACAGCATGCCTGGACACTTTGGGAGCCCTCAGTCC TCAATGTTGGATGATGGGGGCCTACAGGAGGCAGGAGTAAGGAAGAGAGTAGCTCCCCATAAAAGTATAA CAGTATAGAGTGAACACCAAACTACCTCATTTTTCCCATGGGTGAGCTCAGCCCTAGAGGGGTGATGTCT TTGCTTTTTGCATTAATAGCACTTCCAATGTGTTGGGTACCTGAGCAAGAATCCTCAGAAAGACTTTTCT TTTCTTCCATTTTCCTTTTGCTAAACTGCCAAGGATCTCCATCTTTTTAGGGGTTCCAGGTTAGGTTTTT AACCCGTGATGACTCATTTTTATAATGTTCTCTGATTGTGCCTTCATTGCTCCTGTCTCTGCTCTCCTGG ATTCCTGCTACAGGCTAAGGCCACGGAATCTCCAAGTATAGCTGTGGCTGAGTCACTGAACTTTAGTGTT GGTCACTGCCTACTGAAAAAGCTCCATTTCTACCCTCGTATGGGTGCGTGTCCCCACTGCACCCCAAATG GTTATTTCTTTATAGCCAGGCAGCGTGTATGCTGCACCTTGTTTTCAACACCTTTGTGATTCTCCAGTTG CTTTGTTTAAAACTGCTATGAGTTCTATGTATCAGGTACTCTTCAGGGACCTGGGGGCTTATCCCTGAAC TCAGCAGACAGTTTTCCTGACCCAAAGTACAAGGTCTTTGGTCCCTTTCACAAGGAATACAGAGTGTGAT TTAGTTAATTTCCACTACTTGTTTGTTGAATATGGAATAAAGACCTGATTGCTGGCTTTTCCCTTCTTCT CTGATCTCTTTCTTGTATTTTTTATTCCTCCTCCCCCCTTTTATCTACTCTTCCACTGCATTGTCCTCTT TGCTGATGCTACATACTCAGGTCTGTGATTATCATTTCTGTGTCAGTAACTCTTCAGATCTATTTGTCTT GCTCACTTGTATATAATTTCATAGTTCTACCTCCTGACTGGATATCACCAAGTAAATTTGCCAGTTTAGA AGCAAAATATATTTAAAATTCAACTTATCCTCTTCCTCTTACAAGTGTTATTCTTCTAAGATTTATACTT GCTTGAGCACACCTACCCTTTTCCTGGTCATACACTTACATCACCTCTATATTCCAATCAGTGCCCGATC CTCTGAGTTCTATCTTTTAAATTTCTCTCACATCGATGTTCTCTTCTCTTCCTCCTGTCAATACAGCTGA CCAAGTGAAAGCATGGAGATTGCAGGTGCATTTGATAGAAACAGAGAATGGCAAGGGAGGTTAGGGGCAT TTGCAGTGAGGTGGTTTCAGTACAAATCATCAAAACCAAGCTTCATAGTGAGGGAGGTAAAGACAAGCAT GGGATGAAGGATACAAGGGGAAAGGACAAAAGCTTTCAGATTTTTTTCAGTACTGTGAATCGAACCTGAG ACCTGCACACTGAGTTACATCCTTATTCATTTTTAAATTTTTAAATTTTGACACAGTCTCACTAGGTCAC TAAGCTGTCCAGGCTGGGCTCCAGTTTGCAAGCCTCCTGCCTCAGCCTCCCAGAATGCTGGGATTATAAG CATGCTTTGCCATACTCTGCTCAGTTTTGGGATTCTTGATGAGGTGAAAGCTGATTATGGTGTTTGCACT TGACCAGAGAGAATGGAAGTTAAAGAGGTTGTAAGTGGAGCATGAAATGTTCAATGTGGTGGCACAGGCC TGTAATCTCAGCACTTCGGAGGCTGAGGCGAGAGAATCAACATGGTTCAAGGCCAATCTGGGCTACATAG TGAGACCTTGTTTCAAGAAAAGAGAGAGAGAGGGAGAAATGTTTGATTTTGTGATTTGACATCAGTATGG TTTCTGCAATGATGAAGTCTTGCATAAAAGATGAGTGTGTGTGGTTAAAATGTGTGAAAGGAAGAGATAA GTACATTGAGCCTGATGCTGAAATTGTCATCCACATGTGTTTCAGATAACTATAGTCATCTCTTTCCTGA GAAGTCTCTTGGATAGTTCCCTTTTCCAATTTATCTGACCTGATGCTTTCAGCTATACTTTGGACATTGT GACATCCCACTATACACTGAACTATAGGTCAAACTTTAAAATTGCCTTATATTTATTTTATCGTGGGTCA GATAAGGTACTGAATACCTTCCTGAGTCATTTCATCCTTACTCTGTAAAGTAGGCACTGCTATCAATATT TCCATTTATAATCAGGGAACTAAAACAGGCGTAGAAGATTTGTGTAGGTCACTTAGCAAGCGTGAGGCGA ATATTCAGACTCAGTCTGGACTCTTACCCTCTGTCATGTTAACTTAGCATTGGGACTTCCCTTTTTAGTC TTTTTCTCATTCTTAGAGTCACTTTTGCGGAGACCCCAAAGCAAGCAGCAAGTGGGCTCAACTCACTAGG CATGTTGAGAAGTAACTGTGCGCTCACTGCAGACACCTTCTTCACTCTTACATCACCTCTATATTCCAAT CAGTGCCCGATCCTCTGAGTTCTATCTGATCACTCCCAGCACTCGGGAGGCTGAGGCAGCAAGGACTGCC ACGAGTTTGAGGCCAGCATGGGCAACATAAGTGAATTCAAGATCAGCCTGCACTCCACAGTGAGACTATC TCCAAAACACAAAGATCAACAGCAGCAGCAACAACCACAAAACAAAATCCTATCACTTTTTGGAGGTCCC TGAGGAATACTACCTTTTCCACAAGGTTTCCTTCCTTACCAATCCTAAACCCTACCAAACACAGAGCCCT AGGACCTTCCCTTCCTCTGAACCCCCTTAGCTCTTTGTTCATACTCCTCCAAGGCCACCAGAGACATGTC TTTGATGGTAAATTATATAGATGCTATTTCCACTATTAGAATGTTGCCTACAGTGGGGGCAGAAGCTCAA ATTCTTTTCCTTCAAGAACTCAGGAGGAGCTACAAGACTTAGAGGAAGTCAGTGAAGTCAGTGCAGGTTT GTTGATAAACTCTGAGTTGCAAAAGAATGAAGTGATCCATATGTATATATATATATATGGACCAGAATCT AGTTCTCTGAACCCCAGTACAACACTTTCTGCAGTGCCCCCCAACCCTTGTTTCTGCTTCAATTGCTTTC CCTATTTTACCCTTGAAAAGATAGACATATATGGATCTTCTTGACTTTCAGCCCAAATATAAGAGAAAAT CCCTACTGATGATGGTCATGTATACATACTCATAGCTGTGTGTGCACACAGACACAAGACTCTAACTCAT GCTGCTTTGGTTTTTTACCCAGCAATGCTACCTGCAAACCTTTACCCTTCCATTCAGCTCTCCTAACCCT TCCTGACCTGCACTCTGCCTCCACTCAGGATCCCTTCCCCTCACTCTCTCATTCCACTCCTCCACATGAA GCCACAGATCTGTTGTCCTTTTTACATTCTCCTTCTCTTTTGAGATTTGCCTAATAGCAAAAATCTAGAA GACCTAAGTATCAAGCAATAGGGATATATAATAAATCACTGGAGACTCAAATAGTAGAGTGCAGTCATTA AAGATTAAAACATAGCTGGGCACAGTGGTGCAAGCCTATCATTTCAGTTCTCTTGGTGGTTAAGGCAGGA GGATCACAAATTCTAGTCTAACTTGGTCAATTTAGTAACCTAGTGAGACCCTGTCTCAAAAAAAAAAAAA AGCACTGGAAATAGAGCTCAGTACAATTCAATACACAGGACCAACAATCAATAAATCAATCATATAGAAA TACATTAATCTGCTGGGTCTGAAAAATCAGATTAGAAAACACTTTTTCTAGGGTAGTTTAATCTGCTATA TACACATATCTGTATATATATAATCAACATGTCAGATGGCATATATAATCTGTATGTAGACTATATATAT ATATATGAAGAAAATGTAGCAAGATATATATCAAGACAATACTTCTGGCATGCGTATCTTCTATTCTATG TTGATCCTAGGTTACTTGTGAAATCTCTATCTCTCCCCACAAAAGAACAGATCTCACTCTCTGGACAGAC CGACAAAGTTATTTACATACATATGGCCCAACAGAGAACTTTCCAAAGCCATTTTAGTCAGTCAGAAGTG TGAAGTCCTTCCCAAAAGGAAGACCATTTTATGTGATTTCATTACATTTTCTTCTGCTATTGAGGAAGAA ACACTCAGAACTTTTGAAAAGGCACTTCATGGGGGCAGTCCGGGGATGGCCTGGGCAAGAGTTGGTGGAG AGGGGGCTCTGGATCTGGTCAGGCTCTTCTCAGGAAAGATGCTCAGGCCCTTGATGACCTTTGCTTTCTT TCTTACAGCTCCTGTTGCTGGGACCTCTGGTAAGTTCACTGCCTATTTCCTCTCCATCCCCAGCTCCCTC TGTGCTTCTCCCAGTACCCCATTTAGAGATGCTCTGATAGCACTGCAGCCAAGCTCTGTACCAGGAAAGC TCTGTCAGGGCCAGGAAAGGGTCGCCACTCTCAGAAGATGCCCTGCCCACCCCTCCCCTACCCCTATGCA TACAGGCAGTGGACAGCGTGGTCCACAGGTGTTTCAGCCTTCTGGTTCTGTTATGGTGACATGTTGCAGT GTCATAGAAAATGAGAATTCTGCTCTCTTTCAACTGATTTGCACTCTCAAAATCAAGAACTTTGAAAAAA TTGATCTCAAAGAAGTAGAATAGTAGTTAATAGAGCTTGCAAGTGGTAGGGGAGGCTGGAGAGAGGATTT TTAGTGGGTTCAGGGATATAGCTGGATAGGAAGAAAAACTTCTAGTCTTCTGTAGCACAGAAGGGTAACT ATGGTAGACAGCAATTAATAGGTTATTTCAAAATAGCTAGTAGAGAGAATATTTTCTTTTTTGTTGATAG ATGTGATATGACTAATTATATTCATTTTGAGGAATAAATATAGAGATAGCATTCTTTTTGATACTCTTAG TAGAGACAATTTTGAATGTTCTCAAGCAAATAAATGACACACATTTGTAATGTATGGTAGATAGACAACT ATTTTGATCTGATTTTTATAAATTGTATATATGTTAAAGAATTATATGTACCCCATAAATATGTACAGGA ATTACACATCAGAGTTTTTTTTAACTTCGCTAGAGAAAAACAAGGGCTTCTTTCCAAGTAAAATCAAAGC GCATGTAAAATCACGGGATCTGTGCAGACTGTTGTATGTGTTGACAAATTCCTGCTTTGCATGGATCCAA AGGTTCATGGATCCAAGTCCTGTCTCTCTGAGAGGCAGAGCTGTCTTCATATGTTTGGTTGCAGCAAAGT GGACTGAGATTTGTTGGGCACTTCTTTGTCTGTCCTCTGGGCCTCTCACCAACCCCCAGGGCTGACTCTG GAGGCTCCTATGGGCTTGGGAGTGAGGACTGGTGATCCTGACTGCCTTTCTAAGGGATAAAGAATGACAT AGATCAGAGCAGAAACTGATGTCTGACTCTCGGGGCCCACATGTCAGGCAGATGCTGTCACTTGACTTCA GCCAGCTCTTGAAACAGTTTATCCAACCACTGTTCAGATGCCTTGGTTTACAAGGAAGGAAAGTGAGTCC CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAAAGGGAAAGAAAGAG AGAGAGAGAGAGAGAGAGAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAG ACAGAGACAAAGAGAGACAGAGACAGAGGCTCAGAGAGATGCGGGACACACATACAGAGAAGGCTGGGCT ATTTCCTGGTAAGGTAGGATATTTCTAGGGAGTTTCCTTGCCACTCTTCCCCCATCTCTTGTCTTAATCC CAGAGTATGTCCTTGACTCCTGTGGTTGGCTTCAGCTGCAGAAGCTTTCTGGACCTGGTTTCACTCTTGG TACCCATAATGTGAACACAGATGCATCGTTGTCTGAGTTTTAGGGCCTGCTTCAATACCTGGGGCTCCCC TTCCTCATGCTGCCTCTGCTCTCTGCCTCTCAGCAGACCCCCCGAAGGCTGTGGTGAGACTGGAGCCCCC ATGGATCCAGGTGCTCCGGGGAGACCGCGTGACTCTGACCTGCGAGGGTGCCCCCAGCCCTGGGAACCAC TCCACCCAGTGGCTCCACAACGGGAGACTCATCCCTACCCAGGTCCTGCCCAGCTACCGGTTCACTGCCA AGGGCAATGACAGCGGAGAGTACAGGTGCCAGGCGGGCGGGACCAGTCTCAGCGACCCTGTGCGTCTGGA CGTGATTTCTGGTCAGTAGGGCTGGAGAGGCTGGGAGGCCCAGGAGAGGGGAGTCTGCTGATACTGCAGA TGATGGGAGGAAAGGAGGCTGCCTTGATTTCTGGGAAGCACCAGCGTGACTTGCTTGAAGTAATTTTTGC GCACTCATTTCCCTTTCCACCCACTCTTTGGCTTTATATGTGTGGATGGGGGTACGTTTCCTAAGAAGTT TCTCAGCATGTATGAGTAATTGTTTTTGTCTCTCTCCTGCTTGAGCAGGAAGGTTCCAAGGCCACTGACA GGCAACTGGGTATGAGAGAAGCAGAAAGGGGTCTCTGTTTCATAAAAACCCTTTCATTGTCAAGCCAGGC ATGATGACACATCTGTAATCCCAGCATTCAGGGAGGCTAAGGCAGAAGGGTTACAAATTTGAGTCAGGCT TTGCAATTTATCAGTTGAGACAGATCCTGTCTCAGAATAGAAACTAATTAAAAGGCTCTGGATGTAGCCC AATGCGATGGCTCAAGGTTCAATACCCCCCACCACCAAAACACGCAACCATAAATAGACCACAATTTAAT AATCCTAAACCTAGAAATAACCACCTGTATAAACATAATCAGTTTATTAATCCTTAGGTCTAAGTTTCCC CACCTGTTCAACAGAGTTACTAATGTTGCCTTCATAGGGCTTGGGGAGAGCTGGCTCTTCCCTGATCTCC AGCCTCCTTTTCCTACTGGTCTTCATTTTTCTCTCCCTCCAGCACATGGGCAACTTAAAAAGAAAACTGG GTCCTATCCATCTCTGCATTTCCCACATCTGGGACAGGGAAGGGCTTAGTATGTGTTTGCCAAATAGATC AATGATTTTATAAAGCTCCTGGCAGGAAGTAGTTTCCATAATCATTTTCAGATGAAGAAGAGCCATCATC TGGCTAAGTTTATTGTTACTTTTACTCTTTTCTTGGTCCCATCCCTCACTTGATTCTCAAATTTTCCTTA AAAGTATACATCTTAGCCAGGTGTGGTGGCATTCATTTGTAACCCCTGCACTTGGGAGGAAGAAGCAGGA GGATCACTGAATTCAAGGCCAGTATGGGCTACAGAGTGAATTCAAACCCTTCTGTAACTACATGGTGAGA ACCTGTCTCAAAGAAAAAAGTGTACAGTAATTTGTGACACTGCTGCCTTCAGACAAAGTCCCTGTTGACC AGAAGCTCCCCATTTATTCATCAGTATACCAACATCTGTTAGAGTTATAAAACCTTCTATTATCGCCAAA ACATGTCTCTGCTTCACCTGTACCCTCTTCAGTCCCACTGGGACTCAGTCCCAAGGAAGAGATTCTATCT TAGGGTCTCTTGCATATATACTAACAGGACAGGGATGCAACTACCTTCTCTCAGAAAAGGAAAGAGAAGA TGAGTATCCTAACACTCGCTGTATGCCAGGAACTGTTGTAGAGTCCTGGTATTATCATGTTTATTTTAAA GATGAGGAAACTGTGGCACAGACAGTTAAATTATTACCCCAAGATTATAGAGCTCATAGATGAATGGAGC CAGAATTAGAGATCAAGAGTATCTGATTCCAAACTTAGATCCTACCCCCTGCACATTGTGTTCCACTAGA TAGGATAGTCTCAGAGTTGAGTCAAGGCCTCCTGGATCTTGTGGCTCTTGTGTCTTTCAGACTGGCTGGT GCTCCAGACTTCTCAACTGATTTTCCAGGAGGGGGACGTCATCGTGCTGCGGTGCCACAGCTGGAATAAC TGGCCTTTGGCCAAGGTCACATTCTACCACAATGGGGTAGCCAAGAAATATTTCTCTATCAGTAAAAATT TCTCCATCCCACAAGCAAACCACAGTCACAGTGGTGCTTACAACTGCACGGGATTAATAGGAAGGACATC TCACACATCACCGCCTGTGACCATCACTGTCCAAGGTACAGGAACTCTGTCAAGATGTAAAGATAAGAGA AGAGATAATGGACAAGGGTTGAGGTCCTGTAGGCCTGTAAGGAGATCTGAGAAATGCCACACAGCACTGG GGCTGAGGAGAGTTTTTGAAGCTTTGCCCAGTGTTGGCCAGTGGGCAGGAGTAGGGACCAGAGCTCACAG ACATCCACCTCTAGGTATAGGGGACAAGGCTGTGGCCTCATTCTGTGCATAGTAGTAAAGCAGAGCAGCC TCGTTGGCCCACAGCTTTCCTAAGCTCCTAGAATTCTTGAGTGCTGAGGGTGCTGTGTTTCTTCTCCTGT CTCATGGTATGGCCATTTACTCCTGGGGCCTGGTGAGTGCTGAACTGTAGTGACACCTCCAACCAGGGCA GTTCAGATTGCCCACTTTTTTCCCCAGAGAGCTATCTCTCTGCTCCATGTACTCCCCAGCGTGCCTTTAC CTGTGTGGTGGAGAACCTTGGTTCTGGGAGAGGCATAAGTCCAGTCATGGGACCCTCTGCAGATGAGGTT GCAGGGGGAAATGTTATACATGTAAGTGACCAGGATACAGAACAATTTGAAGTGATCAGCACTGTGGTAC AACACTGGGGGGTGTTGAGGCGGGGTAGGGAAATTACTCATCACCTGTCCTCAAATCTAACTTCCCCAGG GCCCAAGTCAAGCGACTCTTCAATGGTGGTGATAATTGTGGCTGCAGTCATTGGGATTGCTACAGCGGCC ATTGTTTTTGCTGTAGTAGCTATCATCTGCCTCAAGAAAAAGCGGCCTCCAGGTTAGTGTCTCTCTCTGG TCCTGCTTGTTATCAATTTCCATTTGGCTAAGGACCTAAGCCCAGGCACTGTCAGACTAGAGAATTATTA GTATTCAACTATCATTCCATTTTTAGTCATTCATTCATTCATTCATTCATTCATTTATTCATTCATCAAG GCTTGAACAGAAAGTCAAGCACTGTGGTAAACACTGGACATGATACCAAGATAAAGGAGCCTAGTCCTTT CTCTCAGAGAATTCTCAGCATATAGGAAAGATATAAATACAAATGGATAATTACAAGATGGATAAGAGCA ATATTAGGGAAGCAAAAAGGCTAGGACAGTGATATAGAAGAGGTGCCATAACCCAGTGTTAGTCAGCTCT TTCACTATAACAAAATACCTGGTATAACCAACTTATAAAGCACAGAGGTTTATTTTTGCTCAGAGATTTG GAGGTTTCAGTCCATGATCAGTTGATCCCATTCCATTAGGCTGTGACTACACAATGTATTATTGCAGGAG CACACCATGGGGCAAAAGTGCTAACCTTATGGCCAGGAAGCAAAGCAGCAAAGAAGAGACCAGGGGTCCC CTAGTCCTCTTCAAGGGCACACCCTCAATGACCTAAAGACCTCCCACTAGACTCTGCCTCTTAATGGTCC CACCATCTTTCAATATTACCAACCTGGGAACCAAGTGTGTCATTCAGGGGACTTTGAGGGACATTTAAGA CATGAATTAAACACCCAGCCTGGGAGGGGACAGTTGGAGAAGGTTTCATGGGGAGGCAATGTACCATAGC AATTGAAAACTACAATTAAGGTCCTGCGGCCCAGCTTCAAATCTCATTTTTTAATTCACCAGCTGTATGA CCTTGGGTGAGTTGCCCAATCTCTCTGTGCCTCAGTTACCTCATCTGAAAAATAGAGACACTCATAGGAC CAACCTCATAGGATTTTTACTATGATGAATGTGGCTGTGAGTCTTATAACAGTTGCCTAATTGGTACTGG CCACACATAAATGTGAGCTGTTACCACTACGGAGGAGGGGATGTTTGCAGAGAATTACCTAGATAAAGAG GGCTGAAAGGGCATTCCAGGCACAGAGGCCAAGGCATGGAGCCAAGGAATGAGAGAATGATACTACTAAT ATCTCACAAAGTTTTGCTGGGGTTCCATAGGGCCCAGTGCCTGATAAGTAAATATTGAGACACTGACATA CTCAGAGAAAGAGGTCTGCTTTAAAAGGCAGAGGAAGCCTAAGAAAGATGGAACCAAGTTGCCTTTCTGC TGCCCTAGAGTTAGCTGACTTTTGTTTCTCTGGACAGTCATTTCACAGACCTGAGTGTCTCCTGGGTGGA GGAGCTGGGAGCTGGGAGGAGCAGAGGCGTCTGTGTGAAGGAAGGGCCTCGTTGATTCTAACCCAACTCT ACCCATGATCCTTGGTTCTGAGGACTCAGGCCCCACCCCATAATCCTACTAACCTCCTCTGTGCCCCTCC TAACTCTCCCAGGAAACCCTGAGCACAGGGAAATGGGAGAAACCCTCCCCGAGGACCCAGGTGAGTACAG CGTTGTCTTTGGGGGCTCAATGATGTCCTGTCCAGGACTGCCAGATGGATTGGAGCCAGCAAGAACTGAC TTGTGTGAGTTTGGCTGGAGCACGTGAGGGGGAGGGGCTGGGAGGAGAGTGGGGCTCAAATCACTTGGTG AGTTCTGAGTCTAACTCCTGGGCCTGAGAAGGGACTCACTGGAGTTAAGAAAACTAGCACTGATTCCAAA TTGAGAAAGGAGAGCTTCACCCACATTTCTGAGGCTAACAATCTGGAGACATTTCCAAAGCAATAAATTA TAGAAATTTGGATCTTTCTGTGGATCCAGATCTGGCAAAACACAGGAGTGAAGTTATAAGAAGGCTAGCA GAATTAAAGAGGCAGGACTCTAAGAGAACAGCGAAAGGAGTTCTGGGAACAACCCCTAGATTTATTGAGG TACTTGTCCCTGTGAAGGGATAGGATGGGCATGGTAGAAACCAACTCTTGGTAGAAAATTAGGAGGAGAT TTGGGCTTAAGAAAATCTGGGGAGCTAGGGCTACAAGTGGGTTTTGTTCTTTGGATAAAACTTGGTTCTG ATGCCAGTCCGTATCAGTGTATTAGATACTGGCCTGGTGCTGCCACCATCATACAATAAAATCTTCCCAT GTTCAGTCACCTCAGTGAGGAAGGAAATGGGTTGGCCTAGACCAACAATGGAGAACCTTTTAGAGATGAG CACCCAAAACTTAAAAACCCGCTTATTTATTGGAAAATGCCAACACTGCAACTAAACCTGAATATTGAGG TTTTAGTTTTGGAAAGAAAAAAAAAACTCATAGTGAACATTTTGTGTCTAAAAAGAAAAACAAATAACAC GTGTGCTATAAATTTGCTACCACTTTGAGCACTGGTATAAAAACCAGTGAATATTCAACCCCTATCCCAA GTGGCAGTGGTGTGAGTATACAAGAAGAGGAGGAGAATGCCAGACCATGTCCTAACCACTGTAAAGGTCA GATTACAAAGGGAACTGGAGCTTTCTCGGGGGACTTCTCTGACAGCAGGATCAGGCAGGAAAATGAGGCC CTTGAATATTGCACCTCATATGGCTGGAGTATGACCTGGGGCAGAGCCAACAGATTTGAGAGCTTGAGCA AACTGTAACTCCTCTAGCTGTGCTTTGAGCCTGCGCTGTCTGTTTCTTGGCCAGGCCATGGGGGGAAGCA CCAAACCAGACCTTTAAGAAAAGTCCAAACACAACTAGATGGTAAATTTACAACTTGTTTGATTCTGCCT ACATTGGCATAAACGCATTTCATCGGAACTGATGTTTTCCCGAAAGATACAGTGAGTCACTGAGGAGTGT GTTAGAAGGGGGACTCCAAGCATGGTTTGTTGCAGAGTTTGGAACATGTCACACAGGACTCTTTGTGTCC AGCAGATGAGGGAAGAGACTAAGAGCATTGTCTCAGACTCCTCCCTGTCTTCCTGGGAAATGCGGATTCA GATACTGAGGCTACTTTTCATTCTGGCAAAGTGATTTATGGCAAAAACATGAGGGAGTTTGGTGTTTTGG GTATTTATCAGAGAAAGTTTTTTTCTTCTTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT CTTTCTTTCTTTCTTTCTCTTTACTTCCTTCCTATCGCTTCTGCCTTTCATCTACATTTTTCTTCTCTCT TCTTGTCTCTTTCTCATCACTTTATTTCTTTTCGATGCCTTGAAGTACCCAATTCTTTACACTTTCAACC AAGATGCACTGAGTTTGAACAGTGTGGAAATGGAAGTTGCTCTTCCCTCCCTGAAGCCTATGGCCAGCAA AAAGACTAGACTTTTGTTTTACTCTGATACTGAACACCCCCACCTCTTTCTCAATCGTTCAGATGCCCAA AGCTGCCTGGTTTGCTTCTAGAAAATCTCACTGATTCTCTACAAATAATGTGGCAAGAATCACTGCTTCC CTGTGGCCAGCGAGAGGCTGAGTCTGGGACAACCCCAGCCTGCATGACTGAGAACAACCATATTGACCTG GCGCTTGGCCTGCAGTCCTAAGTTGGGGTCAGCAGCCTTTGCCTTGGGCCTGTGAACTTTGGTTTTGCAG CTTCAGTGGCAGTACAGGGTGCCTTCTGATCTCGTGGTGCTGGGGCTGATCTCTCTTCTTTTTGTCCACA GCCAATCTCTCTGATCCTGAGGAGGTCGCTAAATCTGAGGTGAGTGATCTCAGCCATCTCCTTGTCCTCT CACCTCTCTTCTCCCCTGCTGTTGTGTTTCTCAAGATCTTTCCTTGGATGTACCACATGTTTCTGCTTTC TCTAGGTTGAAAATACAATCACCTATTCACTTCTCAAGCACCCGGAAGCTCAGGATGATGACACAGAGCA TGACTATCAGAACCACATTTAATCTCCATTATCTGGCCCTGGGATTTGGGGGAGAAAAATCAAGAAGTGA AGATCTGCTATCTCCAGGCCTAAGGTTCCCTTGGAGAGGTCGAGAGGATGCTGAAGTTCAAAGAAGGAGC AGGATTTTTCCAGAGTCCTGTATGTGAGTCCTAAAGTTCTTTGGCCTGACACTAACAGAAAATATGAACT CTGAAGGCTGGCTGATTCTGTGCCTCAGCACTTCCCTACATCAGGGCTGTTATACAGCCCCACAGCCAAC AAAATGATAAAATTAATATTGCTAAGAGATTTTAACAACATGTGACATGCCTACATTATGAGTAACATGA GAAAAATTACATAAGTATATATGATTTCAGAAGTGATAAAATCAACTAACATCTACCAACATATTAAAAA TGATTGTTTCAGGGTGATAGAATTATCAGTGGTTTTTGTTCTTTCTTATTTTCCTACAAATCTATAAGTT TATTTTCCTATAAATCCTATAAATCATGTACTGTATTTGTAATAAAATATTATGAAAA >gi|290543543|ref|NP_001166520.1| low affinity immunoglobulin gamma Fc region receptor II precursor [Cavia porcellus] MAIPSFLPVLGTKSHRADYKPLQTLSHMLLWITVLFLAPVAGTSADPPKAVVRLEPPWIQVLRGDRVTLT CEGAPSPGNHSTQWLHNGRLIPTQVLPSYRFTAKGNDSGEYRCQAGGTSLSDPVRLDVISDWLVLQTSQL IFQEGDVIVLRCHSWNNWPLAKVTFYHNGVAKKYFSISKNFSIPQANHSHSGAYNCTGLIGRTSHTSPPV TITVQGPKSSDSSMVVIIVAAVIGIATAAIVVAVVAIICLKKKQPPGNPEHREMGETLPEDPGEYSVVFG GSMMSCPGLPDGLEPARTDLSNLSDPEEVAKSEVENTITYSLLKHPEAQDDDTEHDYQNHI Vaximmutor ipaB Shigella flexneri 2a VO_0010994 22036246 CDD:293143 42897 ? IpaB 7.76 33839.83 371 Type III cell invasion protein SipB; pfam16535 >AAM89543.1 IpaB, partial (plasmid) [Shigella flexneri 2a] MHNVSTTTTGFPLAKILASTELGDNTIQAANDAANKLFSLTIADLTANKNINTTNAHSTSNILIPELKAP KSLNASSQLTLLIGNLIQILGEKSLTALTNKITAWKSQQQARQQKNLEFSDKINTLLSETEGLTRDYEKQ INKLKNADSKIKDLENKINQIQTRLSELDPESPEKKKLSREEIQLTIKKDAAVKDRTLIEQKTLSIHSKL TDKSMQLEKEIDSFSAFSNTASAEQLSTQQKSLTGLASVTQLMATFIQLVGKNNEESLKNDLALFQSLQE SRKTEMERKSDEYAAEVRKAEELNGV Protective antigen The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) [Ref967:Turbyfill et al., 2000]. IpaC Shigella flexneri 2a VO_0010995 47056 CDD:185271 GOA:P18012 InterPro:IPR005427 UniProtKB/Swiss-Prot:P18012 42897 ? 8.64 40220.05 458 pathogenicity island 1 effector protein SipC; Provisional >CAA33382.1 unnamed protein product (plasmid) [Shigella flexneri 2a] MLQKQFCNKLLLDTNKENVMEIQNTKPTQILYTDISTKQTQSSSETQKSQNYQQIAAHIPLNVGKNPVLT TTLNDDQLLKLSEQVQHDSEIIARLTDKKMKDLSEMSHTLTPENTLDISSLSSNAVSLIISVAVLLSALR TAETKLGSQLSLIAFDATKSAAENIVRQGLAALSSSITGAVTQVGITGIGAKKTHSGISDQKGALRKNLA TAQSLEKELAGSKLGLNKQIDTNITSPQTNSSTKFLGKNKLAPDNISLSTEHKTSLSSPDISLQDKIDTQ RRTYELNTLSAQQKQNIGRATMETSAVAGNISTSGGRYASALEEEEQLISQASSKQAEEASQVSKEASQA TNQLIQKLLNIIDSINQSKNSTASQIAGNIRA Protective antigen The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) [Ref967:Turbyfill et al., 2000]. ipaD Shigella flexneri 2a VO_0010996 22036352 2J0O CDD:297251 42897 ? IpaD 6.14 23805.99 282 Invasion plasmid antigen IpaD; cl05827 >AAM89596.1 IpaD, partial (plasmid) [Shigella flexneri 2a] IRTTNQALKKELSQKTLTKTSLEEIALHSSQISMDVNKSAQLLDILSRNEYPINKDARELLHSAPKEAEL DGDQMISHRELWAKIANSINDINEQYLKVYEHAVSSYTQMYQDFSAVLSSLAGWISPGGNDGNSVKLQVN SLKKALEELKEKYKDKPLYPANNTVSQDQANKWLTELGGTIGKVSQKNRGYGVNINMPPIDNMLKSLDYL GGNGEVVL Protective antigen The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) [Ref967:Turbyfill et al., 2000]. msbB2 Shigella sonnei Ss046 3670926 74315019 SSON_P182 CP000039 YP_313437 300269 pSS_046 159623 160567 + lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase 10.05 34698.04 314 Transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2-(lauroyl)-lipid IVA >gi|74314838:159623-160567 Shigella sonnei Ss046 plasmid pSS_046, complete sequence AATGAAAAAATACAAATCCGAGTTTATTCCTGAATTTAAGAAAAATTATCTTTCCCCTGTTTACTGGTTT ACATGGTTCGTTTTGGGAATGATTGCAGGTATTTCAATGTTTCCCCCTTCATTCAGAGATCCTGTCTTGG CCAAAATAGGGCGTTGGGTGGGCAGATTGAGCAGAAAAGCTCGTCGCAGGGCGACGATTAATTTATCGCT TTGTTTCCCGGAAAAGAGTGATACAGAACGGGAAATAATTGTCGACAATATGTTTGCCACAGCATTGCAA TCCATAGTGATGATGGCAGAACTGGCAATTCGTGGTCCGGAAAAGTTCCAGAAACGAGTGTTCTGGAAAG GCCTCGAAATTCTTGAGGAAATCCGGCACAATAACAGAAATGTGATTTTTCTGGTTCCCCATGGCTGGAG CGTGGATATTCCTGCAATGTTGCTGGCAGCTCAGGGGGAAAAAATGGCCGCCATGTTTCATCAGCAACGA AATCCAGTGATTGATTATGTCTGGAATTCTGTACGGCGTAAATTCGGGGGGCGCTTACATTCCCGGGAGG ATGGGATAAAACCATTTATTCAGTCAGTACGCCAGGGATACTGGGGGTATTACCTTCCAGATCAGGATCA TGGTCCTGAATACAGTGAATTTGCTGATTTTTTTGCGACCTATAAAGCGACATTACCAATTATTGGACGT CTGATGAACATCAGTCAGGCTATGATTATACCGCTTTTCCCGGTTTATGATGAAAAAAAACATTTCCTGA CTATTGAAGTTCGGCCACCAATGGATGCATGCATTGCCAGCGCGGACAATAAAATGATTGCCCGACAAAT GAACAAAACAGTGGAAATTTTGGTGGGGTCACATCCGGAACAGTATATCTGGGTTTTAAAATTGTTAAAA ACGCGCAAATCAAACGAAGCGGACCCGTACCCTTG >gi|74315019|ref|YP_313437.1| lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase [Shigella sonnei Ss046] MKKYKSEFIPEFKKNYLSPVYWFTWFVLGMIAGISMFPPSFRDPVLAKIGRWVGRLSRKARRRATINLSL CFPEKSDTEREIIVDNMFATALQSIVMMAELAIRGPEKFQKRVFWKGLEILEEIRHNNRNVIFLVPHGWS VDIPAMLLAAQGEKMAAMFHQQRNPVIDYVWNSVRRKFGGRLHSREDGIKPFIQSVRQGYWGYYLPDQDH GPEYSEFADFFATYKATLPIIGRLMNISQAMIIPLFPVYDEKKHFLTIEVRPPMDACIASADNKMIARQM NKTVEILVGSHPEQYIWVLKLLKTRKSNEADPYP Virmugen A virG, senA, senB, and msbB2 mutant (WRSs3) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs3 is comparable to live attenuated vaccine strain WRSS1 [Ref2028:Barnoy et al., 2010]. senA Shigella sonnei Ss046 3671021 74314887 SSON_P050 CP000039 YP_313305 300269 pSS_046 46479 48176 + OspD3 6.74 60796.75 565 >gi|74314838:46479-48176 Shigella sonnei Ss046 plasmid pSS_046, complete sequence TATGCCATCAGTAAATTTAATTCCATCAAGGAAAATATGTTTGCAAAATATGATAAATAAAGACAACGTC TCTGTTGAGACAATCCAGTCTCTATTGCACTCAAAACAATTGCCATATTTTTCTGACAAGAGGAGTTTTT TATTAAATCTAAATTGCCAAGTTACCGATCACTCTGGAAGACTTATTGTCTGTCGACATTTAGCTTCCTA CTGGATAGCACAGTTTAACAAAAGTAGTGGTCACGTGGATTATCATCACTTTGCTTTTCCGGATGAAATT AAAAATTATGTTTCAGTGAGTGAAGAAGAAAAGGCTATTAATGTGCCTGCTATTATTTATTTTGTTGAAA ACGGTTCATGGGGAGATATTATTTTTTATATTTTCAATGAAATGATTTTTCATTCCGAAAAAAGCAGAGC ACTAGAAATAAGTACATCAAATCACAATATGGCATTAGGCTTGAAGATTAAAGAAACTAAAAATGGGGGG GATTTTGTCATTCAGCTTTATGATCCCAACCATACAGCAACTCATTTACGAGCAGAGTTTAACAAATTTA ACTTAGCTAAAATAAAAAAACTGACTGTAGATAATTTTCTTGATGAAAAACATCAGAAATGTTATGGTCT TATATCCGACGGTATGTCTATATTTGTGGACAGACATACTCCAACAAGCATGTCCTCCATAATCAGATGG CCTAATAATTTACTTCACCCCAAAGTTATTTATCACGCGATGCGTATGGGATTGACTGAGCTAATCCAAA AAGTAACAAGAGTCGTACAACTATCTGACCTTTCAGACAATACGTTAGAATTACTTTTGGCAGCCAAAAA TGACGATGGTTTGTCAGGATTGCTTTTAGCTTTACAAAATGGGCATTCAGATACAATCTTAGCATACGGA GAACTCCTGGAAACTTCTGGACTTAACCTTGATAAAACGGTAGAACTACTAACTGCGGAAGGAATGGGAG GACGAATATCGGGTTTATCCCAAGCACTTCAAAATGGGCATGCAGAAACTATCAAAACATACGGAAGGCT TCTCAAGAAGAGAGCAATAAATATCGAATACAATAAGCTGAAAAATTTGCTGACCGCTTATTATTATGAT GAAGTACACAGACAGATACCCGGACTAATGTTTGCTCTTCAAAATGGACATGCAGATGCTATACGCGCAT ACGGTGAGCTCATTCTTAGCCCCCCTCTCCTCAACTCAGAGGATATTGTAAATTTGCTGGCCTCAAGGAG ATATGACAATGTTCCCGGACTTCTGTTAGCATTGAATAATGGACAGGCTGATGCAATCTTAGCTTATGGT GATATCTTGAATGAGGCAAAACTTAACTTGGATAAAAAAGCAGAGCTGTTAGAAGCGAAAGATTCTAATG GTTTATCTGGATTGTTTGTAGCCTTGCATAATGGATGTGTAGAAACAATTATTGCTTATGGGAAAATACT TCACACTGCAGACCTTACTCCACATCAGGCATCAAAATTACTGGCAGCAGAAGGCCCAAATGGGGTATCT GGATTAATTATAGCTTTTCAAAATAGGAATTTTGAGGCAATAAAAACTTATATGGAAATAATAAAAAATG AAAATATTACACCTGAAGAAATAGCAGAACACTTGGACAAAAAAAATGGAAGTGATTTTCTGGAAATTAT GAAGAATATAAAAAGCTG >gi|74314887|ref|YP_313305.1| OspD3 [Shigella sonnei Ss046] MPSVNLIPSRKICLQNMINKDNVSVETIQSLLHSKQLPYFSDKRSFLLNLNCQVTDHSGRLIVCRHLASY WIAQFNKSSGHVDYHHFAFPDEIKNYVSVSEEEKAINVPAIIYFVENGSWGDIIFYIFNEMIFHSEKSRA LEISTSNHNMALGLKIKETKNGGDFVIQLYDPNHTATHLRAEFNKFNLAKIKKLTVDNFLDEKHQKCYGL ISDGMSIFVDRHTPTSMSSIIRWPNNLLHPKVIYHAMRMGLTELIQKVTRVVQLSDLSDNTLELLLAAKN DDGLSGLLLALQNGHSDTILAYGELLETSGLNLDKTVELLTAEGMGGRISGLSQALQNGHAETIKTYGRL LKKRAINIEYNKLKNLLTAYYYDEVHRQIPGLMFALQNGHADAIRAYGELILSPPLLNSEDIVNLLASRR YDNVPGLLLALNNGQADAILAYGDILNEAKLNLDKKAELLEAKDSNGLSGLFVALHNGCVETIIAYGKIL HTADLTPHQASKLLAAEGPNGVSGLIIAFQNRNFEAIKTYMEIIKNENITPEEIAEHLDKKNGSDFLEIM KNIKS Virmugen A virG, senA, and senB mutant (WRSs2) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs2 is comparable to live attenuated vaccine strain WRSS1 [Ref2028:Barnoy et al., 2010]. senB Shigella sonnei Ss046 3668265 74313104 SSON_2665 CP000038 YP_311523 300269 2824138 2825313 + putative enterotoxin 7.25 41801.28 391 >gi|74310614:2824138-2825313 Shigella sonnei Ss046 chromosome, complete genome AATGAATATTTTCACTTTATCCAAAGCACCGCTATACCTGTTAATTTCACTATTTTTACCCACGATGGCC ATGGCTATCGATCCACCTGAACGCGAACTTTCGCGATTTGCCCTGAAAACGAATTACCTTCAGTCCCCTG ATGAAGGCGTCTATGAACTGGCGTTTGATAATGCCAGTAAAAAGGTGTTTGCAGCAGTCACCGATCGTGT AAATCGTGAAGCCAATAAAGGCTATCTGTATTCGTTTAATTCAGATTCGCTGAAAGTCGAAAATAAATAC ACGATGCCATACCGGGCATTTTCGCTGGCGATAAATCAGGATAAACATCAGCTCTATATCGGACACACCC AGTCAGCGTCCCTGCGTATCAGTATGTTTGACACCCCAACCGGCAAACTGGTAAGAACCAGCGACAGGTT AAGTTTTAAAGCGGCAAACGCTGCAGATTCGCGTTTTGAGCATTTTCGCCATATGGTTTACAGCCAGGAT TCCGATACCCTGTTTGTGAGTTATAGCAATATGCTGAAAACGGCCGAGGGCATGAAGCCTCTGCATAAGC TGTTAATGCTCGACGGGACGACGCTTGCCTTAAAAGGCGAGGTTAAGGATGCTTACAAAGGTACAGCGTA TGGTCTGACGATGGATGAAAAAACACAGAAAATCTACGTTGGCGGAAGAGATTACATCAACGAAATTGAT GCGAAAAATCAGACGCTGCTGCGTACCATCCCGTTGAAAGATCCGAGACCACAAATCACAAGTGTGCAGA ATCTGGCGGTGGACTCCGCTTCTGACCGTGCCTTTGTGGTGGTATTCGACCATGACGATCGTTCCGGTAC AAAAGATGGACTCTATATTTTTGACTTACGCGACGGTAAACAGCTTGGCTATGTGCACACAGGAGCCGGA GCTAACGCGGTGAAATACAATCCGAAATATAACGAACTGTATGTCACCAACTTCACTAGCGGCACCATCA GCGTAGTGGATGCCACCAAATACAGCATCACCCGTGAATTTAACATGCCGGTCTACCCAAACCAGATGGT GTTGTCGGACGATATGGATACCCTTTACATTGGCATCAAAGAAGGCTTTAACCGCGATTGGGATCCTGAT GTGTTTGTGGAAGGAGCTAAAGAACGTATTCTGAGCATTGATTTGAAAAAGTCGTG >gi|74313104|ref|YP_311523.1| putative enterotoxin [Shigella sonnei Ss046] MNIFTLSKAPLYLLISLFLPTMAMAIDPPERELSRFALKTNYLQSPDEGVYELAFDNASKKVFAAVTDRV NREANKGYLYSFNSDSLKVENKYTMPYRAFSLAINQDKHQLYIGHTQSASLRISMFDTPTGKLVRTSDRL SFKAANAADSRFEHFRHMVYSQDSDTLFVSYSNMLKTAEGMKPLHKLLMLDGTTLALKGEVKDAYKGTAY GLTMDEKTQKIYVGGRDYINEIDAKNQTLLRTIPLKDPRPQITSVQNLAVDSASDRAFVVVFDHDDRSGT KDGLYIFDLRDGKQLGYVHTGAGANAVKYNPKYNELYVTNFTSGTISVVDATKYSITREFNMPVYPNQMV LSDDMDTLYIGIKEGFNRDWDPDVFVEGAKERILSIDLKKS Virmugen A virG, senA, and senB mutant (WRSs2) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs2 is comparable to live attenuated vaccine strain WRSS1 [Ref2028:Barnoy et al., 2010]. virG Shigella sonnei Ss046 3670887 74314980 SSON_P143 CP000039 YP_313398 icsA; S0192 300269 pSS_046 126065 129373 + IcsA/VirG 5.38 111073.91 1102 >gi|74314838:126065-129373 Shigella sonnei Ss046 plasmid pSS_046, complete sequence CATGAATCAAATTCACAAATTTTTTTGTAATATGACCCAATGTTCACAGGGGGGGGCCGGAGAATTACCT ACGGTAAAGGAAAAAACATGCAAATTGTCTTTTTCTCCTTTTGTTGTTGGTGCATCCCTGTTGCTCGGGG GGCCAATAGCTTTTGCTATTCCTCTTTCGGGTACTCAAGAACTTCATTTTTCAGAGGACAATTATGAAAA ATTATTAACACCTGTTGATGGACTTTCTCCCTTGGGAGCTGGTGAAGATGGAATGGATGCGTGGTATATA ACTTCTTCCAACCCCTCTCATGCATCTAGAACTAAGCTACGGATTAACTCTGATATTATGATTAGCGCAG GTCATGGTGGTGCTGGTGATAATAATGATGGTAATAGTTGTGGCGGTAATGGTGGTGACTCTATTACCGG ATCTGACTTGTCTATAATCAATCAAGGCATGATTCTTGGTGGTAACGGCGGTAGCGGTGCTGACCATAAC GGTGATGGTGGTGAGGCTGTTACAGGAGACAATCTGTTTATAATAAATGGAGAAATTATTTCAGGTGGAC ATGGTGGCGATAGTTATAGTGATAGTGATGGGGGGAATGGAGGTGATGCCGTCACAGGAGTCAATCTACC CATAATCAACAAAGGGACTATTTCCGGTGGTAATGGAGGTAACAATTATGGTGAGGGTGATGGCGGTAAT GGAGGTGATGCCATCACAGGAAGCAGCCTCTCTGTAATCAATAAGGGCACGTTCGCTGGAGGCAACGGAG GTGCTGCTTACGGTTATGGTTATGATGGCTACGGTGGTAATGCTATCACAGGAGATAACCTGTCTATAAT CAACAATGGAGCTATTTTAGGCGGTAATGGTGGACATTGGGGGGATGCTATAAATGGTAGCAATATGACC ATTGCTAATAGCGGATATATAATTTCAGGTAAAGAAGATGATGGAACACAAAATGTAGTAGGTAATGCTA TCCACATCACTGGTGGAAACAATTCATTAATACTCCATGAAGGTTCTGTCATTACTGGTGATGTACAGGT TAACAATTCATCCATTCTGAAAATTATCAACAATGATTACACTGGGACCACACCAACTATTGAAGGTGAT TTATGTGCTGGTGATTGTACAACTGTTTCACTATCAGGTAACAAATTCACTGTTTCAGGTGACGTTTCTT TTGGTGAGAACAGTTCTTTAAATTTAGCTGGAATCAGTAGTCTGGAAGCTTCTGGAAATATGTCATTTGG CAACAATGTAAAAGTGGAAGCTATTATAAATAACTGGGCGCAGAAGGACTATAAACTGCTAAGTGCAGAT AAAGGGATAACAGGTTTCAGTGTTTCTAATATATCTATCATCAATCCGTTACTCACTACTGGTGCTATTG ACTATACAAAAAGCTATATCAGTGACCAGAATAAATTGATCTACGGTTTGAGCTGGAATGATACAGATGG CGACAGTCATGGAGAGTTCAATCTGAAAGAAAACGCTGAACTTACTGTTAGTACTATTCTGGCAGATAAT CTCAGCCATCATAATATAAATAGCTGGGACGGAAAATCCCTAACAAAATCAGGGGAGGGAACTCTCATTT TGGCGGAAAAAAATACCTACTCTGGTTTCACCAACATCAATGCAGGCATTCTAAAAATGGGGACAGTTGA AGCTATGACACGTACCGCTGGTGTTATTGTTAATAAAGGTGCTACCTTGAATTTTTCAGGCATGAACCAA ACTGTTAACACTTTATTAAATAGTGGGACTGTGCTAATCAATAATATTAATGCCCCTTTTTTGCCTGACC CCGTCATTGTCACAGGTAACATGACTCTGGAGAAAAACGGTCATGTTATTCTCAATAATAGTTCGTCAAA TGTCGGTCAGACCTATGTTCAGAAAGGTAATTGGCATGGAAAGGGCGGAATATTATCTTTGGGCGCGGTT CTCGGCAATGACAACAGTAAAACTGACCGGCTGGAAATTGCAGGCCATGCGTCTGGTATTACCTATGTTG CAGTGACAAATGAGGGAGGCTCTGGAGATAAAACTCTTGAAGGTGTTCAAATTATTTCGACAGATTCTTC TGATAAGAATGCTTTTATTCAGAAAGGCCGTATTGTTGCTGGTAGTTATGACTATCGCCTGAAACAGGGC ACTGTATCTGGACTGAATACCAATAAGTGGTATCTAACTAGTCAGATGGATAATCAAGAATCAAAACAGA TGAGCAATCAAGAGTCTACTCAAATGAGTAGTCGCCGAGCTAGTTCACAGCTTGTATCTTCACTTAATTT GGGTGAAGGTAGTATTCACACATGGCGCCCTGAAGCTGGCAGTTATATTGCTAACCTGATAGCAATGAAC ACGATGTTTAGTCCTTCTCTCTATGACCGACACGGTAGCACTATTGTTGATCCTACTACAGGTCAGCTCA GCGAAACCACCATGTGGATTCGTACTGTTGGTGGACATAATGAGCATAATTTAGCTGATAGACAATTAAA AACCACAGCTAACAGGATGGTTTATCAGATTGGTGGAGATATTTTGAAGACAAACTTCACTGATCATGAT GGCTTGCATGTGGGTATTATGGGAGCTTATGGATATCAGGATAGCAAAACTCATAATAAGTATACTAGTT ATAGTTCACGAGGAACTGTGAGCGGTTATACTGCCGGTTTGTACAGTTCTTGGTTTCAGAATGAAAAAGA ACGAACAGGTCTATATATGGATGCTTGGTTGCAGTACGGTTGGTTTAATAATACAGTCAAAGGAGATGGG TTAACTGGTGAGAAATATTCCAGCAAAGGAATAACAGGAGCTTTGGAAGCTGGCTATATCTACCCAACCA TACGCTGGACTGCTCATAATAATATTGACAACGCATTGTATCTCAATCCACAAGTCCAGATAACTAGGCA TGGGGTAAAAGCAAACGACTATATTGAACACAATGGCACTATGGTCACATCCTCTGGGGTCAATAATATT CAAGCAAAATTGGGATTGCGTACATCCTTAATTAGTCAGAGTTGTATCGATAAGGAGACTCTTCGTAAGT TCGAACCATTTTTGGAAGTGAATTGGAAATGGAGCTCAAAGCAATATGGTGTAATTATGAATGGCATGTC AAATCACCAGATAGGCAACCGTAATGTGATTGAACTCAAAACTGGTGTGGGGGGGCGTCTTGCAGATAAC CTAAGCATCTGGGGAAACGTATCTCAGCAATTGGGTAATAACAGTTACAGAGACACCCAAGGTATTTTGG GTGTGAAATATACCTTCTG >gi|74314980|ref|YP_313398.1| IcsA/VirG [Shigella sonnei Ss046] MNQIHKFFCNMTQCSQGGAGELPTVKEKTCKLSFSPFVVGASLLLGGPIAFAIPLSGTQELHFSEDNYEK LLTPVDGLSPLGAGEDGMDAWYITSSNPSHASRTKLRINSDIMISAGHGGAGDNNDGNSCGGNGGDSITG SDLSIINQGMILGGNGGSGADHNGDGGEAVTGDNLFIINGEIISGGHGGDSYSDSDGGNGGDAVTGVNLP IINKGTISGGNGGNNYGEGDGGNGGDAITGSSLSVINKGTFAGGNGGAAYGYGYDGYGGNAITGDNLSII NNGAILGGNGGHWGDAINGSNMTIANSGYIISGKEDDGTQNVVGNAIHITGGNNSLILHEGSVITGDVQV NNSSILKIINNDYTGTTPTIEGDLCAGDCTTVSLSGNKFTVSGDVSFGENSSLNLAGISSLEASGNMSFG NNVKVEAIINNWAQKDYKLLSADKGITGFSVSNISIINPLLTTGAIDYTKSYISDQNKLIYGLSWNDTDG DSHGEFNLKENAELTVSTILADNLSHHNINSWDGKSLTKSGEGTLILAEKNTYSGFTNINAGILKMGTVE AMTRTAGVIVNKGATLNFSGMNQTVNTLLNSGTVLINNINAPFLPDPVIVTGNMTLEKNGHVILNNSSSN VGQTYVQKGNWHGKGGILSLGAVLGNDNSKTDRLEIAGHASGITYVAVTNEGGSGDKTLEGVQIISTDSS DKNAFIQKGRIVAGSYDYRLKQGTVSGLNTNKWYLTSQMDNQESKQMSNQESTQMSSRRASSQLVSSLNL GEGSIHTWRPEAGSYIANLIAMNTMFSPSLYDRHGSTIVDPTTGQLSETTMWIRTVGGHNEHNLADRQLK TTANRMVYQIGGDILKTNFTDHDGLHVGIMGAYGYQDSKTHNKYTSYSSRGTVSGYTAGLYSSWFQNEKE RTGLYMDAWLQYGWFNNTVKGDGLTGEKYSSKGITGALEAGYIYPTIRWTAHNNIDNALYLNPQVQITRH GVKANDYIEHNGTMVTSSGVNNIQAKLGLRTSLISQSCIDKETLRKFEPFLEVNWKWSSKQYGVIMNGMS NHQIGNRNVIELKTGVGGRLADNLSIWGNVSQQLGNNSYRDTQGILGVKYTF Virmugen A virG mutant (WRSS1) is attenuated in guinea pigs and induced significant protection from challenge with wild type Shigella sonnei [Ref871:Hartman and Venkatesan, 1998]. Altboum et al., 2001 journal Altboum Z, Barry EM, Losonsky G, Galen JE, Levine MM 2001 69 5 3150-3158 Infection and immunity Barnoy et al., 2010 journal Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, Venkatesan MM 2010 28 6 1642-1654 Vaccine Chakrabarti et al., 1999 journal Chakrabarti MK, Bhattacharya J, Bhattacharya MK, Nair GB, Bhattacharya SK, Mahalanabis D 1999 88 2 161-165 Acta paediatrica (Oslo, Norway : 1992) Coster et al., 1999 journal Coster TS, Hoge CW, VanDeVerg LL, Hartman AB, Oaks EV, Venkatesan MM, Cohen D, Robin G, Fontaine-Thompson A, Sansonetti PJ, Hale TL 1999 67 7 3437-3443 Infection and immunity Gupta et al., 2011 journal Gupta P, Singh MK, Singh Y, Gautam V, Kumar S, Kumar O, Dhaked RK 2011 29 45 8094-8100 Vaccine Hartman and Venkatesan, 1998 journal Hartman AB, Venkatesan MM 1998 66 9 4572-4576 Infection and immunity Hartman et al., 1991 journal Hartman AB, Powell CJ, Schultz CL, Oaks EV, Eckels KH 1991 59 11 4075-4083 Infection and immunity Heine et al., 2014 journal Heine SJ, Diaz-McNair J, Andar AU, Drachenberg CB, van de Verg L, Walker R, Picking WL, Pasetti MF 2014 192 4 1630-1640 Journal of immunology (Baltimore, Md. : 1950) Kärnell et al., 1993 journal Kärnell A, Cam PD, Verma N, Lindberg AA 1993 11 8 830-836 Vaccine Klee et al., 1997 journal Klee SR, Tzschaschel BD, Fält I, Kärnell A, Lindberg AA, Timmis KN, Guzmán CA 1997 65 6 2112-2118 Infection and immunity Kotloff et al., 1992 journal Kotloff KL, Herrington DA, Hale TL, Newland JW, Van De Verg L, Cogan JP, Snoy PJ, Sadoff JC, Formal SB, Levine MM 1992 60 6 2218-2224 Infection and immunity Kotloff et al., 2000 journal Kotloff KL, Noriega FR, Samandari T, Sztein MB, Losonsky GA, Nataro JP, Picking WD, Barry EM, Levine MM 2000 68 3 1034-1039 Infection and immunity Kotloff et al., 2002 journal Kotloff KL, Taylor DN, Sztein MB, Wasserman SS, Losonsky GA, Nataro JP, Venkatesan M, Hartman A, Picking WD, Katz DE, Campbell JD, Levine MM, Hale TL 2002 70 4 2016-2021 Infection and immunity Kotloff et al., 2004 journal Kotloff KL, Pasetti MF, Barry EM, Nataro JP, Wasserman SS, Sztein MB, Picking WD, Levine MM 2004 190 10 1745-1754 The Journal of infectious diseases Kotloff et al., 2007 journal Kotloff KL, Simon JK, Pasetti MF, Sztein MB, Wooden SL, Livio S, Nataro JP, Blackwelder WC, Barry EM, Picking W, Levine MM 2007 3 6 Human vaccines Malaei et al., 2013 journal Malaei F, Hesaraki M, Saadati M, Ahdi AM, Sadraeian M, Honari H, Nazarian S 2013 10 2 110-117 Iranian journal of immunology : IJI Marteyn et al., 2010 journal Marteyn B, West NP, Browning DF, Cole JA, Shaw JG, Palm F, Mounier J, Prévost MC, Sansonetti P, Tang CM 2010 465 7296 355-358 Nature Niyogi, 2005 journal Niyogi SK 2005 43 2 133-143 Journal of microbiology (Seoul, Korea) Noriega et al., 1994 journal Noriega FR, Wang JY, Losonsky G, Maneval DR, Hone DM, Levine MM 1994 62 11 5168-5172 Infection and immunity Noriega et al., 1996 journal Noriega FR, Losonsky G, Lauderbaugh C, Liao FM, Wang JY, Levine MM 1996 64 8 3055-3061 Infection and immunity Oany et al., 2017 journal Oany AR, Pervin T, Mia M, Hossain M, Shahnaij M, Mahmud S, Kibria KMK 2017 2017 6412353 Journal of immunology research Orr et al., 1993 journal Orr N, Robin G, Cohen D, Arnon R, Lowell GH 1993 61 6 2390-2395 Infection and immunity Orr et al., 2005 journal Orr N, Katz DE, Atsmon J, Radu P, Yavzori M, Halperin T, Sela T, Kayouf R, Klein Z, Ambar R, Cohen D, Wolf MK, Venkatesan MM, Hale TL 2005 73 12 8027-8032 Infection and immunity Osorio et al., 2007 journal Osorio M, Bray MD, Walker RI 2007 25 9 1581-1592 Vaccine Pore and Chakrabarti, 2013 journal Pore D, Chakrabarti MK 2013 31 36 3644-3650 Vaccine Sansonetti et al., 1991 journal Sansonetti PJ, Arondel J, Fontaine A, d'Hauteville H, Bernardini ML 1991 9 6 416-422 Vaccine Shim et al., 2007 journal Shim DH, Chang SY, Park SM, Jang H, Carbis R, Czerkinsky C, Uematsu S, Akira S, Kweon MN 2007 25 25 4828-4836 Vaccine Turbyfill et al., 1995 journal Turbyfill KR, Joseph SW, Oaks EV 1995 63 10 3927-3935 Infection and immunity Turbyfill et al., 2000 journal Turbyfill KR, Hartman AB, Oaks EV 2000 68 12 6624-6632 Infection and immunity Venkatesan et al., 2002 journal Venkatesan MM, Hartman AB, Newland JW, Ivanova VS, Hale TL, McDonough M, Butterton J 2002 70 6 2950-2958 Infection and immunity