Campylobacter jejuni 197 Most Campylobacter infections are mild, self-limiting diarrheal illnesses, but severe infections do occur. The primary risk factors associated with Campylobacter infection are consuming and handling foods of animal origins, especially poultry products. In addition to epidemiological evidence, microbiological evidence supports poultry as the primary source of human Campylobacter infection (Nelson et al., 2007). The majority of Campylobacter-associated infections are thought to be sporadic cases of food poisoning; contaminated drinking water, including that from public water supplies, is the vehicle of large Campylobacter-associated outbreaks. Although Campylobacter spp. are widely distributed in the environment, the epidemiology of many cases of Campylobacter-associated infections remains unclear (Abulreesh et al., 2006). After incubation of approximately three days, abrupt cramping pain in the abdomen is followed by diarrhea. The mechanism of diarrhea induction is a complex and multifactorial process. The diarrheal stage lasts a few days. Complications are rare, but infection may be followed by the development of reactive arthritis or GBS. Flagella-mediated motility has been shown to be necessary for Campylobacter to colonize the intestinal tract, and experimental infections in humans and animals, and in vitro analyses of adherence and invasion in cultured human cells have demonstrated that cell invasiveness is necessary in Campylobacter-induced inflammatory diarrhea. Several bacterial components have been shown to have adhesive properties (LPS, flagella, fimbrial filaments, surface-exposed proteins), and a direct role of toxins including of cytolethal distending toxin (CDT) in disease remains to be demonstrated. Host factors are of importance in the pathogenesis of GBS following a Campylobacter infection. It is now clear that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies (Engberg, 2006). Campylobacterosis Anti-flagellar serum antibody titres of the dams did not correlate with protection of their young (Dolby et al., 1986). There was a good correlation between high campylobacter-specific IgG response and bactericidal activity. The degree of protection conferred by vaccinated dams on infant mice against colonization by Campylobacter jejuni depended on the bacterial strain, preparation, and route of administration of the vaccine. In some instances of homologous protection, serum bactericidal titres correlated well with protection. However, boiled C. jejuni vaccine, which was non-protective, also elicited a strong bactericidal antibody response. Conversely, bactericidal activity could not be demonstrated against strains capable of cross-protection. (Abimiku et al., 1989). The primary risk factors associated with Campylobacter infection are consuming and handling foods of animal origins, especially poultry products. In addition to epidemiological evidence, microbiological evidence supports poultry as the primary source of human Campylobacter infection (Nelson et al., 2007). Campylobacter jejuni is a small gram-negative, microaerophilic, motile, curved-to-spiral rod that has a single polar flagellum. It can be found in the intestinal tract and oral cavity (Smibert, 1978). C. jejuni is among the most frequent causes of bacterial diarrhea worldwide and an important cause of diarrhea in travellers and deployed military personnel. It is also the infectious agent most often associated with Guillain-Barre syndrome (GBS), a postinfectin polyneuropathy, and is increasingly identified as a cause of bacteremia and a variety of systemic and localized infections in immunocompromised hosts. The bacteria is characterized by a lack of understanding of the basic virulence mechanisms and by its antigenic complexity. The LPS cores of many serotypes have been shown to contain structures which resemble human gangliosides and have been implicated in the development of autoantibodies leading to GBS, although the specific structure or structures which enable a given campylobacter strain to cause GBS are not clear (Lee et al., 1999)(Pawelec et al., 2000). 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 Avirulent Salmonella vaccine strain carrying C. jejuni cjaA gene VO_0004121 Recombinant vector vaccine The constitutive expression of all analysed genes as measured by Western immunoblot technique was independent of the particular host strain. Specific rabbit anti-rCjaA antibody reacted not only with CjaA but also with other solute-binding proteins, components of the ABC transport system (CjaC protein), chosen as the protective antigen for animal experiments. Chickens orally immunized with Salmonella expressing Campylobacter cjaA gene developed serum IgG and mucosal IgA antibody responses against Campylobacter membrane proteins and Salmonella OMPs. Protection experiments show that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduces ability of heterologous wild type C. jejuni strain to colonize the bird cecum (Wyszynska et al., 2004). The heat-labile enterotoxin of Escherichia coli as an oral adjuvant ( OA ) has been used (Baqar et al., 1995). The vaccine vector is avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004). Three gene libraries of Campylobacter jejuni 72Dz/92 DNA were prepared using lambda gt11, pSupercos and pWSK129 cloning vectors. Screening of the libraries revealed several immunoreactive clones (Pawelec et al., 1997). Three C jejuni genes [cjaA ( cj0982c ) , cjaC ( cj0734c ) and cjaD ( cj0113 )] encoding highly immunogenic proteins which are conserved among different Campylobacter serotypes have been introduced into avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004). C. jejuni 72Dz/92 cjaA gene encodes a highly immunogenic protein which is conserved among different Campylobacter serotypes (Wyszynska et al., 2004). The surface antigen CjaA of Campylobacter jejuni is supported by the presence of an upstream gene with significant homology to ATP binding proteins (Martin et al., 1999). Recombinant vector construction pUWA10A plasmid carrying CjaA was ligated into the pYA3341 plasmid and then transformed into E. coli χ6097 competent cells. It was later introduced by electroporation into two S. enterica sv. Typhimurium (χ3987 and χ4550) strains (Wyszynska et al., 2004). Mucosal anti-Salmonella and anti-Campylobacter IgA antibodies were present in samples taken from chickens inoculated with Salmonella/pUWM251 at every tested time point. In contrast to serum IgG, the kinetics of IgA responses to both antigens were similar. In intestinal secretions the level of the antibodies dropped at week 2 and then peaked 2 weeks after the booster. During the next 2 weeks, IgA titers decreased and maintained at almost the same level during the remainder of the experiment. Since IgA antibodies directed towards both antigens were present in the intestinal fluids of 1-day-old birds, similarly to IgG antibodies, IgA present at 0 week were maternally derived. In intestinal secretions, taken from different parts of chicken gut (rectum and jejunum), levels of IgA antibodies to Campylobacter and Salmonella antigens also peaked 2 weeks after the secondary immunization. Intestinal IgA titers to Campylobacter whole cell lysates followed the similar patterns as those measured with membrane antigens (Wyszynska et al., 2004). Commercial broiler chickens (Gallus gallus) Commercial broiler chickens were obtained from the local hatchery on the day of hatch. Briefly, chickens deprived of food and water for 4 h were immunized orally with 100 μl of 109 CFU/ml of Salmonella χ3987 carrying pUWM251 (cjaA). Booster doses were administrated 2 weeks after primary immunization. Following vaccination, chickens were observed for the development of diarrhoea and other potential adverse side effects (Wyszynska et al., 2004). There was high anti-Campylobacter IgG titer present at the first time point (week 0), dropping at weeks 2 and 4. A moderate increase of Campylobacter specific IgG level was observed at week 6 followed by significant increase of anti-Campylobacter IgG level at week 8. Serum IgG titers to Campylobacter whole cell lysates followed a similar pattern, as those measured with membrane antigens, with respect to time, although the increase of anti-Campylobacter IgG titer at week 8 was not so significant. The results suggest that high IgG titer observed at the 0 week reflects maternally derived immunity while increasing serum IgG titers at 6 and 8 weeks is a consequence of vaccination (Wyszynska et al., 2004). Protection experiment showed that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduced the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004). No adverse side effects were observed (Wyszynska et al., 2004). Two weeks after booster, all chicks received a dose containing approximately 2×10^9 CFU/ml of the wild type C. jejuni/pUOA18 strain in 0.1 ml PBS with gelatine. Campylobacter colonization was confirmed on days 3, 6, 9 and 12 after the challenge. In each instance, four chicks were euthanized, the intestine was excised and the C. jejuni present in chicken cecal contents were enumerated by plating (Wyszynska et al., 2004). It is well documented that poultry and poultry products are the major source of human campylobacteriosis and salmonellosis. The avirulent Salmonella vaccine strains expressing Campylobacter antigen can be potentially used as a bivalent chicken vaccine (Wyszynska et al., 2004). C. jejuni DNA vaccine pcDNA3.1(+)-cadF VO_0011545 DNA vaccine Research pcDNA3.1(+) [Ref1038:Zheng et al., 2007] Intranasal Intranasal C. jejuni fibronectin binding protein cadF DNA vaccine construction The chitosan-DNA vaccines was prepared by embedding pcDNA3.1(+)-cadF with chitosan (Zheng et al., 2007). BALB/c BALB/c mice were intranasally immunized in a four-dose primary series (7 d intervals) at doses of 60 microg chitosan-DNA vaccines each time (Zheng et al., 2007). The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. Moreover the chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70. The results of this study indicate that the chitosan-DNA vaccines could induce significant protective immunity against C. jejuni challenge in the mice model (Zheng et al., 2007). Mice were attacked repeatedly through intragastric administration of C. jejuni HS:19 at the 8th week after the immunization and protective efficacy was determined by detecting the degrees of protection afforded against C. jejuni invaded (Zheng et al., 2007). C. jejuni DNA vaccine pcDNA3.1(+)-peblA VO_0011488 DNA vaccine Research pcDNA3.1(+) [Ref1038:Zheng et al., 2007] Intranasal Intranasal C. jejuni bifunctional adhesin/ABC transporter aspartate/glutamate-binding protein DNA vaccine construction The chitosan-DNA vaccine was prepared by embedding pcDNA3.1(+)-peblA with chitosan (Zheng et al., 2007). The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87, respectively (Zheng et al., 2007). BALB/c BALB/c mice were intranasally immunized in a four-dose primary series (7 d intervals) at doses of 60 microg chitosan-DNA vaccines each time (Zheng et al., 2007). The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 (Zheng et al., 2007). Mice were attacked repeatedly through intragastric administration of C. jejuni HS:19 at the 8th week after the immunization and protective efficacy was determined by detecting the degrees of protection afforded against C. jejuni invaded (Zheng et al., 2007). C. jejuni FlaC protein vaccine VO_0011495 Subunit vaccine Research Intranasal LTR192G Intranasal C. jejuni flagellin subunit protein FlaC Recombinant protein preparation The flaC gene from C. jejuni 81-176 was expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008). BALB/c Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008). FlaC provided an 18% protection against disease from C. jejuni 81-176 (Baqar et al., 2008). Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008). C. jejuni FspA1 protein vaccine VO_0011485 Subunit vaccine Research Intranasal LTR192G Intranasal C. jejuni flagellum-secreted protein FspA1 Recombinant protein preparation The fspA1 gene from C. jejuni 81-176 was expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008). BALB/c Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008). Immunization with FspA1 resulted in 57.8% protection without adjuvant or 63.8% protection with adjuvant against homologous challenge with 81-176 (Baqar et al., 2008). Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008). FspA1 induced significantly high levels of serum immunoglobulin G (IgG) in mice 18-20 days after 3rd vaccination. These results are compared to PBS vaccinated mice (Baqar et al., 2008). FspA1 induced significantly high levels of fecal IgA in mice 7 days after last vaccination. These results are compared to PBS vaccinated mice (Baqar et al., 2008). C. jejuni FspA2 protein vaccine VO_0011487 Subunit vaccine Research Intranasal LTR192G Intranasal C. jejuni flagellum-secreted protein FspA2 Recombinant protein preparation The fspA2 gene from C. jejuni CG8486 were expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008). BALB/c Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008). Immunization with FspA2 provided 38.4% (without adjuvant) or 47.2% (with adjuvant) protection against disease from homologous challenge with CG8486 (Baqar et al., 2008). Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008). C. jejuni MBP-FlaA protein vaccine VO_0011493 Subunit vaccine Research Intranasal Mutant E. coli heat-labile enterotoxin (LT(R192G)) Intranasal C. jejuni structural flagella protein flaA and maltose-binding protein MBP Recombinant protein preparation Purification schemes were essentially as recommended by NEB. DH5α containing the flagellin-MBP fusion was grown overnight in 10 ml of rich medium (10 g of tryptone, 5 g of yeast extract, 5 g of NaCl, and 2 g of glucose/liter) supplemented with 100 μg of ampicillin per ml and used to inoculate a fresh 1-liter culture of the same medium. This culture was grown with shaking at 37°C to an optical density at 600 nm of 0.5, and IPTG (isopropyl-β-d-thiogalactoside; Gibco, Gaithersburg, Md.) was added to a final concentration of 0.3 mM (Lee et al., 1999). BALB/c Mice were anesthetized with methoxyflurane (Metofane; Pitman-Moore, Mundelein, Ill.) and immunized intranasally with 30 to 35 μl of fusion protein by using a micropipette. The doses used were 0, 3, 6, 12, 25, or 50 μg of fusion protein in phosphate-buffered saline (PBS), either alone or in combination with 5 μg of the genetically modified heat-labile enterotoxin of E. coli, designated LTR192G as an adjuvant. A second dose was administered 8 days after the first vaccination (Lee et al., 1999). The protective efficacies of a 50 microgram of MBP-FlaA plus LT(R192G) dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10^10, 8 x 10^9, or 8 x 10^8 cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively (Lee et al., 1999). Mice were intranasally challenged with 2 × 10^9 C. jejuni bacteria/mouse 26 days after the second vaccination, and the animals were monitored for sickness and death for 5 days (Lee et al., 1999). The full range of MBP-FlaA doses were effective in eliciting significant antigen-specific serum immunoglobulin G (IgG) responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. The results were compared to PBS vaccinated mice 7 days after immunization (Lee et al., 1999). Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA (>/=25 microgram) or coadministration of lower doses with the adjuvant. IgA titers were significant 7 days after immunization as compared to PBS-vaccinated mice (Lee et al., 1999). C. jejuni PorA protein vaccine VO_0004203 Subunit vaccine Research orally a modified heat-labile enterotoxin of Escherichia coli toxin, LT R192G (Islam et al., 2010) orally Recombinant PorA protein Recombinant protein preparation BALB/c BALB/c mice were orally vaccinated twice at a weekly interval with the purified GST-PorA fusion protein combined with a modified heat-labile enterotoxin of Escherichia coli toxin, LT R192G, as an adjuvant. Mice immunized with LT R192G or PBS (pH 7.2) alone were included as controls. Vaccination was done by using a stainless steel, curved-ball-tip feeding needle (20 gauge, 1.5-in. long; Popper and Sons, Inc., New Hyde Park, NY). Just prior to vaccination, gastric acidity was neutralized with two doses (0.5 ml each) of a 5% sodium bicarbonate (pH 8.5) solution given as an oral gavage at an interval of 15 min. An amount of 300 µg of the GST-PorA fusion protein mixed with 5 µg of LT R192G in a total volume of 300 µl in PBS (pH 7.2) was given to each of nine animals. Another group of mice was each fed with 5 µg of LT R192G and yet another group each fed with 1x PBS (pH 7.2) (Abimiku et al., 1989). (Islam et al., 2010) The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline (Islam et al., 2010). Mice were challenged with bacterial culture 3 weeks after the second vaccine dose, immediately after tail vein blood collection. A 48-h bacterial culture grown on campylobacter agar was suspended in PBS (pH 7.2) to a concentration of 2 x 109 CFU per ml, and 0.5 ml of the suspension was orally fed to the mice immediately after neutralization of the gastric acidity (Islam et al., 2010). deltaphoP/Q S. typhimurium strains expressing PEB1-ss VO_0004124 Recombinant vector vaccine PEB1, the major cell-binding factor of Campylobacter jejuni, is a homolog of the binding component in Gram-negative nutrient transport systems (Prokhorova et al., 2006). PEB1 is an adherence factor that is highly immunogenic in humans (Sizemore et al., 2006). Three live, attenuated deltaphoP/Q Salmonella enteric serovar Typhimurium strains expressing PEB1 minus its signal sequence (PEB1-ss) from three different plasmids were prepared. The three plasmids include a pBR-based asd plasmid, an arabinose-based runaway plasmid, which each expressed PEB1-ss in the bacterial cytosol, and a PEB1::HlyA fusion plasmid that directs secretion of PEB1-ss into the extracellular milieu (Sizemore et al., 2006). Campylobacter PEB1 is an adherence factor that is highly immunogenic in humans (Sizemore et al., 2006). Serum IgG responses specific for PEB1-ss were induced by pBR-derived and runaway plasmids, with 100 and 90% seroconversion, respectively, at a 1:500 dilution of anti-sera as measured by Western blot analysis, while the PEB1-ss::HlyA fusion plasmid induced serum IgG in only 20% of the mice (Sizemore et al., 2006). Female, BALB/c Mouse Specific Pathogen Free (MSP) 7–9 weeks of age from Taconic Mice that had been acclimated for 5 days were vaccinated with freshly prepared inocula on days 1 and 12 of the experiment by pipet feeding. The target concentration for this experiment was 1–2.5E8 in 50 μl (Sizemore et al., 2006). MGN4735 was able to colonize the intestine to a high level over the entire test period of 9 days post-inoculation while those mice that survived challenge with 81-176 cleared the infection (Sizemore et al., 2006). Although significant levels of anti-PEB serum IgG were induced, no protection against oral Campylobacter jejuni challenge was observed (Sizemore et al., 2006). no adverse side effects were observed Challenge of vaccinated BALB/c mice was based on the model developed by Baqar et al. (Baqar et al., 1995b). C. jejuni strain 81-176 served as the challenge strain in the oral model (Sizemore et al., 2006). Three live attenuated ΔphoP/Q Salmonella enteric serovar Typhimurium strains expressing PEB1 minus its signal sequence (PEB1-ss) from three different plasmids: a pBR-based asd plasmid, an arabinose-based runaway plasmid, which each expressed PEB1-ss in the bacterial cytosol, and a PEB1::HlyA fusion plasmid that directs secretion of PEB1-ss into the extracellular milieu are described above (Sizemore et al., 2006). Inactivated C. jejuni whole-cell (CWC) VO_0004100 Inactivated or "killed" vaccine Whole-cell vaccine formulations deserve further evaluation as candidate vaccines and the potential value of mucosal adjuvants, like LT, in enteric vaccine development are not in doubt (Baqar et al., 1995). 25 mg of a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) has been used (Baqar et al., 1995b). Volunteers given the CWC vaccine have similar IgA-ASC and sIgA responses and in vitro induction of IFN to Campylobacter antigens (Walker, 2005). The CWC vaccine is prepared from the 81-176 strain of C. jejuni and consists of a 1:1 mixture of heat (60 C, 60 min)- and formalin (0.02 M)-inactivated Campylobacter whole cells. Each vaccination group receives oral doses of CWC vaccine containing bacterial cells alone or in combination with 25 mg of LT. Just prior to vaccination, gastric acidity is neutralized by 2 doses of a 5% NaHCO3 solution (pH 8.5) with a 15-min interval (Baqar et al., 1995b). inactivated whole-cell Campylobacter jejuni (CWC) Campylobacter-specific intestinal IgA responses are dependent on the use of LT, whereas IgA and IgG responses in serum are not. Intestinal lavage fluid collected from sham-immunized animals at 7 d post-vaccination have no detectable levels of Campylobacter- or LT-specific secretory IgA (sIgA) or IgG. When CWC is administered over a 10,000-fold range of doses, only 20% of the mice immunized with the low or intermediate doses mount a significant Campylobacter-specific sIgA response. In contrast, administering the same doses with LT resulted in a substantial enhancement of the sIgA response to vaccine-associated Campylobacter antigens in all vaccination groups (Baqar et al., 1995b). BALB/c Mice were orally immunized in a three-dose primary series with CWC vaccine particles alone or in combination with a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) (Baqar et al., 1995b). Ninety percent of control animals remain colonized for 9 days post-challenge. A similar colonization pattern is observed in mice vaccinated with LT alone. Clearance of challenge organisms from mice receiving CWC vaccine alone appear to be dependent on the amount of vaccine administered. Although 80% of the mice receiving the highest vaccine dose cleared the infection within 3 days of challenge, the remaining 20% were colonized for the remainder of the study period (Baqar et al., 1995b). Colonization resistance was induced over a broad range of vaccine doses when LT was included. However, only the highest dose of CWC alone gave comparable levels of protection. Both formulations provided equivalent protection against systemic spread of challenge organisms. These results indicate that both whole-cell vaccine formulations deserve further evaluation as candidate vaccines and also highlight the potential value of mucosal adjuvants, like LT, in enteric vaccine development (Baqar et al., 1995b). Both the CWC and CWC-LT vaccine formulations are well tolerated, with no weight loss or signs consistent with toxicity in immunized animals. Histopathological examination of the intestinal mucosa and other organ systems following vaccination fails to detect evidence of tissue damage or severe inflammation (Baqar et al., 1995b). At ~4 wks post-vaccination, mice were challenged orally with C. jejuni, and duration of colonization was determined by the monitoring of fecal shedding. Efficacy was determined by measuring the degree of protection afforded against intestinal colonization and systemic dissemination of challenge organisms (Baqar et al., 1995b). Inactivated Campylobacter whole-cell vaccines (CWC) must be given orally in large doses to be effective. Drawbacks could be overcome by the coadministration of LT (Baqar et al., 1995b). Antibodies generated during natural infection in ferrets by either strain 81-176 or strain VC167 appeared to react more strongly to glycosylated flagellins isolated from Campylobacter spp . than to unglycosylated , recombinant flagellins isolated from E coli . (Lee et al., 1999) Mustela putorius furo Food was withheld prior to challenge. The vaccine dose was administered orally via a pediatric nasogastric tube. After 60 min, animals were administered paragoric i.p. to slow peristalsis. Drinking water was supplemented with tetracycline for three days prior to rechallenge to decrease the competing intestinal microflora (Burr et al., 2005). An oral regimen delivered on days 0, 3, 5, and 7 provided enhanced protection following oral homologous challenge delivered at Days 0 and 14. The percent protection observed was 100% in previously infected ferrets, 50% in a two-dose CWC group, and 89% in a four-dose CWC group. Protection was afforded through vaccination with sufficient inactivated whole cell vaccine, but protection was obtained regardless of the inclusion of the adjuvant LTR192G (Burr et al., 2005). Ferrets show some conservation of protection against disease induced by Campylobacter. Upon rechallenge, homologous protection was 67-84%. Heterologous challenge resulted in 67-80% protection. These data indicate that the strain chosen for use in humans protects against disease caused by two of the major serotypes responsible for human disease (Burr et al., 2005). Following infection, animals were monitored three times daily for signs of diarrhea, dehydration, appetite and water consumption. Rectal swabs from each ferret were cultured for C. jejuni by direct plating on C. jejuni selective agar. At the appropriate time, blood samples were obtained by bleeding the animals from the jugular vein while under light anesthesia using acepromazine-ketamine. Collected sera were assayed for specific anti-Campylobacter immunoglobulin levels. At the conclusion of each experiment, animals were lightly anaesthetized with acepromazine-ketamine then euthanized by intracardiac injection of sodium pentobarbital (Burr et al., 2005). Food was withheld prior to challenge. Animals received ketamine plus acepromazine i.m. Following sedation, the vaccine or challenge dose was administered orally. Animals being fed live organisms were administered paragoric i.p. For secondary challenge the procedure was otherwise identical, except that NaHCO3 was delivered prior to challenge. In addition, drinking water was supplemented with tetracycline prior to rechallenge. All challenge doses were monitored by plate counts (Burr et al., 2005). The strong IgG responses seen upon rechallenge of vaccinated or previously challenged animals may not be protective in themselves but could indicate the magnitude of other unmeasured antibody responses following immunization. Whatever the exact nature of the protective immune responses associated with the CWC vaccine, it is clear that the vaccine offers protection which may be relatively conserved among clinically important serotypes of Campylobacter (Burr et al., 2005). Chickens orally immunized developed serum IgG and mucosal IgA responses against Campylobacter membrane proteins, as measured by an ELISA test. Protection experiments show that chicken immunization greatly reduces the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004). A hybrid protein was administered as a vaccine to chickens either orally or i.m. Alimentary secretions were collected , and specific antibodies were assayed by western blot analyses (Khoury et al., 1995). Seventy-two percent of the birds vaccinated orally with 1000 micrograms protein showed detectable antibodies against C jejuni flagellin in the excreta . None of the control birds produced detectable antibody to this antigen (Khoury et al., 1995). The nature of the antibody response to MOMP during in vivo infection is not well understood. Antibody responses elicited in Campylobacter-colonized chickens demonstrates that proteoliposomes restore reactivity to rabbit antibodies. Sera from naturally or experimentally infected chickens reacts weakly, suggesting that the chicken antibody response is predominantly directed against conformational epitopes. These observations provide direct evidence for conformation-dependent humoral responses induced by Campylobacter infection, demonstrate that C jejuni is immunogenic in its natural host and suggest that proteoliposomes may be potentially used for the evaluation of vaccines (Huang et al., 2007). No adverse side effects have been associated with this vaccine in chickens. For trials to demonstrate clearance of Campylobacter, groups of chickens were vaccinated with the hybrid protein at 2 and 4 wk of age and challenged at 3 wk with an excess of Cjejuni. The number of birds that remained colonized at 5 wk of age was significantly lower among the vaccinated birds than among controls (Khoury et al., 1995). This is a conserved immunodominant protein in this organism and a promising vaccine candidate because the protein is expressed in multiple Campylobacter isolates from both chicken and human hosts (Martin et al., 1999). licensed Campylobacter infection human vaccine Generic Unknown VO_0012182 Subunit vaccine Licensed A generic representation of vaccines utilized to prevent Campylobacter infection in humans, typically composed of purified antigens or proteins derived from Campylobacter species. These vaccines aim to elicit protective immune responses without using whole pathogens. MBP fused on Campylobacter FlaA (MBP-FlaA) VO_0004101 Conjugate vaccine A mucosal vaccine was used in an effort to elicit serum IgG and intestinal secretory IgA. A genetic hybrid of the Campylobacter jejuni flaA gene with LT-B of Escherichia coli and assessment of the efficacy of the hybrid protein has been developed an oral chicken vaccine (Wilkinson et al., 2003). immunization occurs with the mutant E. coli heat-labile enterotoxin (LT( R192G)) as a mucosal adjuvant (Lee et al., 1999) The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum IgG responses, and these responses were enhanced by adjuvant use. Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA or coadministration of lower doses with the adjuvant (Lee et al., 1999). Part of the flaA gene ( 780 base pairs ) was cloned in plasmid pBEB downstream and in frame with the LT-B to allow expression of a hybrid protein . Transformed E coli chi 6097 expressed the hybrid protein ( 43 kdaltons ) in inclusion bodies at mid log phase . The inclusion bodies were isolated , and the identity of the protein was verified by western blot . (Khoury et al., 1995) recombinant protein comprising the maltose-binding protein (MBP) of E. coli fused to amino acids 5 to 337 of the FlaA flagellin of Campylobacter coli VC167 (Lee et al., 1999) flagellin protein Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA or co-administration of lower doses with the adjuvant (Lee et al., 1999). BALB/c Mice were immunized intranasally with two doses of 3 to 50 mg of MBP-FlaA, given 8 days apart, with or without 5 mg of the mutant E. coli heat-labile enterotoxin (LTR192G) as a mucosal adjuvant (Lee et al., 1999). The results showed that, when challenged with bacteria, there was a reduction in colonization as early as 3 days after infection and that no campylobacter organisms could be detected in stools by 7 days post-feeding (Lee et al., 1999). The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum IgG responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. When vaccinated mice were challenged intranasally 26 days after immunization, the best protection was seen in animals given 50 mg of MBP-FlaA plus LTR192G. The protective efficacies of this dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized intranasally were challenged orally with 8 x 10^10, 8 x 10^9, or 8 x 10^8 cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively (Lee et al., 1999). Animals were monitored for sickness and death for 5 days and only minimal adverse side effects were encountered (Lee et al., 1999). Mice were intranasally challenged after the second vaccination. Fecal excretion of C. jejuni was monitored daily for 10-14 days after challenge by culturing fecal homogenates. Putative colonies were confirmed by morphology and oxidase reactions. Mice were challenged orally with 0.5 ml of various doses of C. jejuni. Fecal excretion was monitored as described above for 7-9 days (Lee et al., 1999). It is interesting that antibodies generated during natural infection by either strain 81-176 or strain VC167 appear to react more strongly to glycosylated flagellins isolated from Campylobacter spp. than to unglycosylated, recombinant flagellins isolated from E. coli. Immunization with the recombinant fusion protein lacking post-translational modifications may lead to antibody production against epitopes which are less immunogenic in the native molecule due to differences in folding and/or masking by the carbohydrate moiety but are, nonetheless, capable of eliciting a protective immune response. Further evaluation of this recombinant flagellin is ongoing as a vaccine in a ferret diarrheal disease model (Lee et al., 1999). cadF Campylobacter jejuni VO_0011044 WP_002851185 CDD:275358 CDD:225439 CDD:143586 194 ? fibronectin-binding outer membrane protein CadF 5.71 36447.78 419 outer membrane beta-barrel protein; TIGR04565 >WP_002851185.1 MULTISPECIES: fibronectin-binding outer membrane protein CadF [Campylobacter] MKKIFLCLGLASVLFGADNNVKFEITPTLNYNYFEGNLDMDNRYAPGIRLGYHFDDFWLDQLEFGLEHYS DVKYTNTNKTTDITRTYLSAIKGIDVGEKFYFYGLAGGGYEDFSNAAYDNKSGGFGHYGAGVKFRLSDSL ALRLETRDQINFNHANHNWVSTLGISFGFGGKKEKAVEEVADTRATPQAKCPVEPREGALLDENGCEKTI SLEGHFGFDKTTINPTFQEKIKEIAKVLDENERYDTILEGHTDNIGSRAYNQKLSERRAKSVANELEKYG VEKSRIKTVGYGQDNPRSSNDTKEGRADNRRVDAKFILR Protective antigen Chitosan-DNA vaccines were prepared by embedding pcDNA3.1(+)-cadF and pcDNA3.1(+)-peblA with chitosan respectively. The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 [Ref1038:Zheng et al., 2007]. cjaA Campylobacter jejuni RM1221 VO_0010955 3231573 1813949 CJE1064 CP000025 YP_179057 CDD:270412 GOA:P94643 InterPro:IPR001638 UniProtKB/TrEMBL:P94643 197 993662 994501 - surface antigen, CjaA 4.9 29158.88 324 Substrate binding domain of ABC cysteine transporter; the type 2 periplasmic binding protein fold; cd13694 >NC_003912.7:993662-994501 Campylobacter jejuni RM1221, complete genome ATTAAATTTTTCCACCTTCAATCACTACATCATCAGCCTTAACATCATCTCCAAAATGAGCTTTTAAAGT TTCATCATAAGCCTTGTGAAAAAACTGCTCTTGGCCTAGTTTAATGATCAAATTATCGATAAATTCTTTA AGTTCTTTATCGCCTTTTTTAACCGCTGGTGCGATAACATCTTTGTTACCTAACTCTTTGATACCCATTT TAAAATCAGGATGATCTTTCACCCAAGCAAAAAGCAAGGTATTATCATGACTTAAAGCATCGCCTCTTTT ATCCATCAAAGCGGCAAAGGTTTCGGTATTTTGATCATATTTTAAAGTTTTAATATTAGGATAATTTTGC GTAAAATAAGCATCTGCTGTTGTACCTTTGTTTAAAAGCAAGGTTTTATCTTTTAAATCTTCTACGCTAG TTATATTACTATCCTTTGGTACAGCTACGCCTAAAGCTACCTTCATATAAGGCAAGCAAAAATCAACCTG TTCTGCCCTTTGCGGAGTTTGAGTAAAATTAGCCAAAATAATATCTACTTTATTTGATTTTAAAAACTCA ACCCTATTTGCAGCTTCAACAAGAACAAATTGCACCTTATTTTCATCGCCAAAAAGTTCTTTTGCTATGC GTTTAGCTAAAGCTATATCATAGCCTTGATTGTTTCCTTTTTCATCTACATAACCAAAAGGTGGTTTATC GCCAAATACCCCAATCCTAACAACTCCATTTTGCTTGATCTTATCAAGAGAATTTAAAGTTTTAGAGTCA GAATTTCCTCCACAAGCAGCCAATACTACTGCAACAAAGGTCGTTAAAACACTTAGAAGTATTTTTTTCA >CAA71822.1 cjaA [Campylobacter jejuni] MKKMLLSIFTTFVAVFLAACGGNSDSGASNSLERIKQDGVVRIGVFGDKPPFGYVDEKGVNQGYDIVLAK RIAKELLGDENKVQFVLVEAANRVEFLKSNKVDIILANFTQTPERAEQVDFCLPYMKVALGVAVPQDSNI SSIEDLKDKTLLLNKGTTADAYFTKEYPDIKTLKYDQNTETFAALIDQRGDALSHDNTLLFAWVKEHPEF KMAIKELGNKDVIAPAVKKGDKELKEFIDNLITKLGEEQFFHKAYDETLKSHFGDDVKADDVVIEGGKI Protective antigen A total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium DeltaaroA vaccine expressing the C. jejuni amino acid binding protein CjaA. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4log(10) colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA [Ref1036:Buckley et al., 2010]. FlaA from C. jejuni 81-176 Campylobacter jejuni subsp. jejuni 81-176 VO_0011046 4682159 121612545 CJJ81176_1339 AY102622 YP_001000997 354242 1255199 1256929 - flagellin 5.37 56366.68 576 FlaA; structural flagella protein; in Helicobacter the flagella are composed of flagellin A and flagellin B; the amounts of each seem to be controlled by environmental conditions >NC_008787.1:1255199-1256929 Campylobacter jejuni subsp. jejuni 81-176, complete genome ACTATTGTAATAATCTTAAAACATTTTGCTGACTAGAATTTGCTTGAGCCATTGCATAAGAACCACTTTG GGCTAAGATGTTAGCTTTAGAGTAGTTTGCACTCTCACTTGCAAAGTCTACATCTCTGATTTGCGATTCT GCTGCTTTAACATTAACTTGAGTTACAGTAATGTTATTTATAGTTGATGTAACTTGATTTTGTATAGAAC CAATATCTGCTCTGATTTGATCTAGATTTGTTATAGCAGTTTCTGCTATATCCATAACCGCCATTGCACC TTTAAGAGTGGTTACACCTGCAGTCTCATCAGTTGTATTAGCAGCAGTAGTTTTAAGGGCTGCAAATTGA GAATTTCCTGAGCCAGAAGAAAATCCTGAACCTGCTGAAACAACATAAGTATTGCTCATTGAAGCCGCAC TTGAAATAATTTGTATTCCTTGACTCAATCCAACAGATAAATTTTTACCACTACCCACAGAAAATCCTGA ACCTCTAGAAAATCCTGAACCTTGTGCACTCATAAATGCAGAAATTGAACTTACATTTTGAGTAAAAACA AATTTTCCACCACCTTTATAAGAATTAAATCCCATAGCATCGGCATTGGTTGCTGAAATTTGACCTTTTG ATTCTCTTAAAGACACTGAAGATTGAGAAATCATATCTGTTGTACCCATACCTATAGCACTAAGATTGGT TCCACTTATATTGATATCTCTACCATCATTTTTAACTAAAGATAATCGCCCATAGTTTTCTTTTTGATTT GCCAAAATACCAGAACCAACACCTATATCTCCAGTAATTTTAATACCCCTGCCATCAGCCGATGTAAGAA CAAGCTTGCCGTTTTCATCTTTAGAAGCTTGAACTCCTGTGGTATCTTTAACCGCATTGATAGCTGAAAT CAAAGAGCCGTTACCATCTCCGTCTTTGTATTCAATTTTTCCTATAGTTACTCCATTAATGGCAAATTCT TGAGAAGTAGTTCCTTCTTTTATAGCATAAACGCCAGTTGTTTTTACATCGTAAGTTGCGCGAACTCCTG TTTTATCAGCGCTTTTATTGATCTCTTCAGCCAAAGCTCCAAGTCCTGTTCCAACTGAAGTTGAAATCAC AACATTATCAAATTTAAAATCTTCTATACCATTGTAGTTTTTAATAGTAAGACCAACCACACCTGAAGTA AAACTTTGAGCACCGGTTTCAAATCTTGTAACACCGATTTTAGAAGATTGAGTAGCACCGATAGTTGCTT TCACAGTTTGGTTTGAACTTGCGCCGATTTGGAATTCTTGATTGGTAAAATTTCCACTTAAAAGTTGCTT ACCATTAAATGAAGTAGTATTTGCGATATTATCAAGCTCTTCCATTAATTTATTAATATCTGCTTGAAGC ATAGTTCTTGTTTTTAAACTTTGTCCATCTTGAGCTGCTTGAGTAGCTTTAGTCTTGATAGTATCAAGAA TTTTTAATTGCTCATCCATAGCTTTATCTGCGGTTTGTAAGATACCTAAAGCATCATTACCATTTGATAT AGCTTGACCTAAAGTATTTGCTTGAGATCTTAAGCTATCTGCTATCGCCATCCCTGAAGCATCATCTGCT GCTGAGTTAATTCTAAGACCTGAACTAAGTCTGCTTAAAGAAGCATCTAAACTTTTAGCATTAAGATCAG AGTTTGCTTTTGCATTCAATGCTGCAACATTTGTGTTAATACGAAATCCCA >YP_001000997.1 flagellin [Campylobacter jejuni subsp. jejuni 81-176] MGFRINTNVAALNAKANSDLNAKSLDASLSRLSSGLRINSAADDASGMAIADSLRSQANTLGQAISNGND ALGILQTADKAMDEQLKILDTIKTKATQAAQDGQSLKTRTMLQADINKLMEELDNIANTTSFNGKQLLSG NFTNQEFQIGASSNQTVKATIGATQSSKIGVTRFETGAQSFTSGVVGLTIKNYNGIEDFKFDNVVISTSV GTGLGALAEEINKSADKTGVRATYDVKTTGVYAIKEGTTSQEFAINGVTIGKIEYKDGDGNGSLISAINA VKDTTGVQASKDENGKLVLTSADGRGIKITGDIGVGSGILANQKENYGRLSLVKNDGRDINISGTNLSAI GMGTTDMISQSSVSLRESKGQISATNADAMGFNSYKGGGKFVFTQNVSSISAFMSAQGSGFSRGSGFSVG SGKNLSVGLSQGIQIISSAASMSNTYVVSAGSGFSSGSGNSQFAALKTTAANTTDETAGVTTLKGAMAVM DIAETAITNLDQIRADIGSIQNQVTSTINNITVTQVNVKAAESQIRDVDFASESANYSKANILAQSGSYA MAQANSSQQNVLRLLQ Protective antigen Mice were immunized intranasally with two doses of 3 to 50 microgram of MBP-FlaA. The protective efficacies of a 50 microgram of MBP-FlaA plus LT(R192G) dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10(10), 8 x 10(9), or 8 x 10(8) cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively [Ref197:Lee et al., 1999]. FlaA from C. jejuni NCTC 11168 Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 VO_0010942 905631 218562948 Cj1339c AL111168 YP_002344727 BioCyc: CJEJ192222:CJ1339C-MONOMER EMBL: AL139078 InterPro: IPR001029 InterPro: IPR001492 InterPro: IPR010810 KEGG: cje:Cj1339c Pfam: PF00669 Pfam: PF00700 Pfam: PF07196 PIR: H81277 PRINTS: PR00207 ProDom: PD000316 UniProt: P56963 192222 1269231 1270949 - flagellin A 5.36 55763.1 572 flaA, flagellin A, len: 572 aa; 80.7% identity to FLAA_CAMJE flagellin A (575 aa), fasta scores; opt: 2816 z-score: 2717.6 E(): 0, 80.7% identity in 575 aa overlap. 48.3% identity to HP0601. Also similar to Cj1338c (flaA), Cj0720c flaC (24.5% identity in 220 aa overlap), and Cj0887c flaD (20.2% identity in 560 aa overlap). Contains fam match to entry PF00669 Flagellin_N, Bacterial flagellin N-terminus, and Pfam match to entry PF00700 Flagellin_C, Bacterial flagellin C-terminus. The flaA and flaB genes have a GC content of 37% compared to the overall genome GC content of 30.5% FUNCTION: Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella (UniProt: P56963) SUBUNIT: Heteropolymer of flaA and flaB (UniProt: P56963) SIMILARITY: Belongs to the bacterial flagellin family (UniProt: P56963) >NC_002163.1:1269231-1270949 Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 chromosome, complete genome ACTACTGTAGTAATCTTAAAACATTTTGTTGAACAGAATTAGCCTGTGCCATGGCATAAGAGCCGCTTTG AGCTAAGATATTTGCTTTAGAGTAGTTTGCACTCTCGGCTGCAAAGTCTACATCACGGATTTGCGATTCT GCTGCTTTAACGTTTACTTGAGTTACGGTGATGTTGTTTATAGTTGATGTAACTTGATTTTGTACCGAAC CAATGTCGGCTCTGATTTGATCAAGATTTGTTATAGCTGTTTCAGCTATATCCATCACAGCCATAGCGCC TTTAAGTGTGGTAACACCTGCTGTTTCATCTTTTACTCCAAAAGCAGTTGTTTTCATAGTTGCAAACTGA GAAAGTGTTGAACCACTTGAAAAACCTGAGCCTGCAGAAACATTATATACCGTAGAAAGTTGCGAAGCAG CTGAAATAGCTATAGCGTTTGCAAAACCTGTGGAATAATTTTTACCGCTACCTACAGAATAACCTGAACC TGAAGAAAATCCACTTCCTGCGCTACTCATATAGGCACTAACAGAAGAATAACCACCTAACACAACTCCT TTGTTTGCAGAACCAAATCCCATAGCATCAGCGATATTAGCATCAATTTGTCCTTTTGACTCTCTTAAAG AAACAGAAGCTTGAGAGATAAATTGAGTTGCACCAAAACCTGCAGAAGAAAGATTGCTACCGCTGATTAA AATATCTTTACCATCATTTTTAACTAAAGACAAGCGGCCATAGTTTTCTTTCATATCAGCATTGATAAAG GCACCTCCACCTATATTACCATCGATTTTAATCCCTCTACCTTCTCTTGAAGTAAGTAAAAGTTGTCCAT TAGCATCGATCGAAGCTTCAACTCCAGTGGTATCTTTAACCGAATTGATTGCAGCAACTAAGGCTCCATT AGCATCACCATCTTTGTAATCTACTTTACCGATTTTTACCCCATTGATAGCAAAAGTATCTGAAGTAGCT CCTGCTCTAACTGCAGCTATACCTCTAGTTTCTACTGTAAAAGTAGCTCTAACACCTGTTTTATCAGCAT TTTTATTGATCTCATCTGCTAAAGCTCCAAGTCCTGTTCCAACTGAAGTTGAAATCACAACTTTTTGAAA CTGAAAATCATCTATACCATTGTAATTTTTAAGAGTAAATTGTACTTCGCCACTAGTTGAAATTCTTCCT CCTGTTTCAAAGCGTGTTAAACCTATCTTAGAAGATTGAGTTGCTCCTATAGTAGCTTTTACAGTTTGAT TTGAACTTGCACCGATTTGAAATTCTTGATTGATAAAATTCCCACTTAAAAGTTGTTTACCGTTAAATGA AGTAGTATTTGCAATATTGTCAAGTTCTTCCATTAAACGGTTGATATCTGCTTGAAGCATGGTTCTTGTT TTTAAACTTTGTCCATCTTGAGCCGCTTGAGTTGCCTTAGTTTTGATTGTATCTAAGATTTTAAGTTGCT CATCCATAGCCTTATCAGCAGTTTGTAAGATACCTAAAGCATCATTACCATTAGATATAGCTTGACCTAA AGTATTAGCTTGAGATCTTAAACTATCTGCTATCGCCATCCCTGAAGCATCATCTGCTGCGGAGTTGATT CTAAGACCTGAACTAAGTCTGCTTAAAGAAGCATCTAAACTTTTACTATTTAAATCAGCGTTTGCTTTTG CATTTAAAGCTGCAACATTGGTGTTAATACGAAATCCCA >YP_002344727.1 flagellin A [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819] MGFRINTNVAALNAKANADLNSKSLDASLSRLSSGLRINSAADDASGMAIADSLRSQANTLGQAISNGND ALGILQTADKAMDEQLKILDTIKTKATQAAQDGQSLKTRTMLQADINRLMEELDNIANTTSFNGKQLLSG NFINQEFQIGASSNQTVKATIGATQSSKIGLTRFETGGRISTSGEVQFTLKNYNGIDDFQFQKVVISTSV GTGLGALADEINKNADKTGVRATFTVETRGIAAVRAGATSDTFAINGVKIGKVDYKDGDANGALVAAINS VKDTTGVEASIDANGQLLLTSREGRGIKIDGNIGGGAFINADMKENYGRLSLVKNDGKDILISGSNLSSA GFGATQFISQASVSLRESKGQIDANIADAMGFGSANKGVVLGGYSSVSAYMSSAGSGFSSGSGYSVGSGK NYSTGFANAIAISAASQLSTVYNVSAGSGFSSGSTLSQFATMKTTAFGVKDETAGVTTLKGAMAVMDIAE TAITNLDQIRADIGSVQNQVTSTINNITVTQVNVKAAESQIRDVDFAAESANYSKANILAQSGSYAMAQA NSVQQNVLRLLQ Protective antigen FlaC Campylobacter jejuni subsp. jejuni 81-176 VO_0011048 4682885 121612344 CJJ81176_0743 CP000538 YP_001000416 354242 671962 672711 - flagellin subunit protein FlaC 4.32 25481.71 249 identified by match to protein family HMM PF00669 >NC_008787.1:671962-672711 Campylobacter jejuni subsp. jejuni 81-176, complete genome ATTATTGTAATAAATTAGCAATTTTGCTTTGAAGCTGCATGTTGGATTGCGCAGCAACAAAAGCAGCAGC ATTTTCTTTTAGATAATTGGCATTAAAATCATTAACATTTTTTGCCATATCATTATTTAGTAAATTATTT TCAGCTGCTTTTGAGTTGATGCTATTTTGAACACTTGCATTAATATTTGATGTAATGGCATTGATACCTG AACCTATTTCACTTCTTAAACTTCCAAGTTGATCCATAAAATTTGTAATACTATCTTGATTATCTATGCT TAATCCACCTGTTGCTAATGGATTTAAATTTGTAGTTTCAGTTCCGCTACCTACTACAAAATTCATAGTT TGAAAGACATTTTTTCCATTATAAGTTGCATTATTAAAAGAATTATTGATGGATTCTTGTATGCGTGTTG CTTCTGTTCTTAGCATTCCTTTTTGAGAATCATTAAGTGCAGCATTGTTCATTTTTACTGAAAGTTCATT AAGTCTATCTGCGCTTTGAGAGATATTGGTAAGGCTAGCATCTGCAATTTGTAAAACCCCTATAGCATCA TAAGCATTTGCGACACCTTGATCTATAGTGCTTGATTGAGATCTTAAAGAATCAGCAATAGCTAAATTAG CACTATCAACTCCACTTATTGCGCGAACAGCTGCAATATTTTCTAAAGCTTTATCGCTAGCTTTTTGTGC ATTATTTAAATAATAATTTTGTTGCATCATAGTTGCATCAGAGATCATCA >YP_001000416.1 flagellin subunit protein FlaC [Campylobacter jejuni subsp. jejuni 81-176] MMISDATMMQQNYYLNNAQKASDKALENIAAVRAISGVDSANLAIADSLRSQSSTIDQGVANAYDAIGVL QIADASLTNISQSADRLNELSVKMNNAALNDSQKGMLRTEATRIQESINNSFNNATYNGKNVFQTMNFVV GSGTETTNLNPLATGGLSIDNQDSITNFMDQLGSLRSEIGSGINAITSNINASVQNSINSKAAENNLLNN DMAKNVNDFNANYLKENAAAFVAAQSNMQLQSKIANLLQ Protective antigen Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. All three proteins were immunogenic, FlaC provided an 18% protection against disease from C. jejuni 81-176 [Ref1039:Baqar et al., 2008]. fspA1 Campylobacter jejuni VO_0011047 116292649 CDD:330552 197 - FspA1 4.34 15410.38 187 exonuclease subunit SbcC; Provisional; cl25731 >ABJ97640.1 FspA1 [Campylobacter jejuni] MQINNSLNSLSQYVKVNSNEENQNSKNQEQNALAQDPAVEVNISKEAKEKSNASNQNNSQAPAQALNAQN NTQQDSSSNSEDKLTELTQKLAEIQAKIVELTAKMSKANEDQIKSIESQIATLNAQASTIQAQIQELQSQ QA Protective antigen Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. Immunization with FspA1 resulted in 57.8% protection without adjuvant or 63.8% protection with adjuvant against homologous challenge with 81-176 [Ref1039:Baqar et al., 2008]. fspA2 Campylobacter jejuni VO_0011049 116292677 197 ? FspA2 5.78 15654.3 187 sigma 28 regulated; Campylobacter jejuni-specific virulence factor that is secreted through the flagella filament >ABJ97654.1 FspA2 [Campylobacter jejuni] MKIDTLTKNFSNYQTQINKNNDLASNVHSDNVVKIQISDEARSLSQANSKNEKEYEIKVSQEKIENHKDQ NSIQSSKGGGNPALEALIAKLAEILAKIAELTQKMTNANEQMKTTFQKQIDVLISQADVIQAQIQELQSQ QA Protective antigen Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. Immunization with FspA2 provided 38.4% (without adjuvant) or 47.2% (with adjuvant) protection against disease from homologous challenge with CG8486 [Ref1039:Baqar et al., 2008]. IgA Mus musculus 238447 AC160982 10090 12 8607 12639 - immunoglobulin heavy constant alpha Also known as IgA; Igh-2 >gi|121699722:8607-12639 Mus musculus immunoglobulin heavy chain complex (Igh) on chromosome 12 AGTACTGGGGGACCTCTTTGCTGCCAAACGGGCCTCGAACAGTTGTAACAGTGAGTGCTGTGCTGTAGAA CAAGCTCAGTAGGAAGAGGGTGAGGAAGGTCACAGTGGTGGGCCACAGGCTGGCACCTGGGGCCTCTTCC TCCAGGATGTCTTCTGACTGGTCCAGTAGCACATAGGAAAGTGGCTCTTGACGTTCTGTAAGACATAGAT GACCTTCTAGATCCAAACCCATGGGGATGGGGGCTCAGACTTAAGGTTTCTGCTTCTATGCCTCCTTGGG CTTTGGGGACAGTGGTGGTAGGGGTCCCTTATTCCCGGGAAGGGACTTGTTCAGGGATAATGAGGAGGCA GGGTCCCAGGTAAGGGACTGGAATCCCAGCAGTTCTTGAGATGGCCCCAAGACCCATCTCTCTCTCTTAG GGAAACCTTAATTAGAGACCTGTCATGGTAAGAGAGTTGTTTCTGTCAAACTCTGAGAAGAGTTTGAACC CAAGGCTCCTTAGGTCTCAGTCCTTTCTAGATATTTAGCAATACCTCCCTAAACCCCAGTTCTTAGGCTA ATCTTGGCTTGGGTACTAGGGTTGTGTAAGATCAGACACCTTCAAACAGATACAGGCCAATGTGATTTCT GGGCCAAAGTTAGACTACCAAGGCCTGGACATGTGGTCAGAGGACTCTGTTGCATTCTTAAGAGCTGTGA CTGGGGGTTAAGCAACAGTAAAGACCCCCAGTAGAGCCAACCCTGCTGTCCTCAGGTTCTCTGCGCACAG AGTTTCATTTTAAGTGGCAGTAGGAAATGTGTACTGATAGTCAACCACTCGTATTTCTGTCACTGCAGCC ATCCATCAATCCATCCATCATCCCCATCGTTCATCCTTGTAGCCAGCCATCCATTACCCTCCAGCCGCTC ACTCATCATCTTTCCCGACTATCGTGATTCTCCAGCTTCTCTGCCCCCTCTCCCTGTGGGGATTCAGTCT TTCACCTATTGACTCCTCCTTACTAGGATTCTCTGTCATGGGCCAGGCCTTGGATTCCATGGGTGGCTAT GGTACTTTTCTGAGTCAGGTTTCCCAAGCTGGTCTGTTGCTCTTGCTATTCTCAGGGAACTGGACTTTCA AGCTGGAGAGTATCCAGGGCATGCATGGGCCTTTACTCCACTCTTGCTCTGAGAGCAGAGGGAAGTTGCT AGAAACCAGCAACTCCTCCCCCCCCCCCCCGAAGTTCTGAAGGCCTGTGAGACAGGAGCAGGGCCCCCAC TGCCCTCTTGTGGACACCTGGGCTCCAAGTATACCTGGTTGTAGAACTTTGTGTTCTAGGGGTGCCCATG GAGGAGGCCGAGGCCTGTGTGGGAGTGGTCTCCATGGCCTGCTCCTGCTTCTTCCCAGATTTGCCTCTTA TCCTGCTTCTGGTTTGTGATACTTGGGCTCAGGATGGGAAGGGAGACTTAGGTTAGAAAGGGGGCACCTG GAGGGGCCTATGCCCTTGTCCATTGTGTGTAGTTGTCAGTGTCGGGCCTGGAAATTCTCCCGGGGGCTTG GAGGGGACTCCCCTTGCTTTCCAGAAGCTGGGTGTGGGCTGTGAACTTCATCTTCCTCCAGGGTTCAGGT CTGTGTGAGTGTGCAAATGTGAGTGTCTGTGCATGTATGCCCATGTGCATGTATGCAGAACAGGGTGTAT GCCCATGTGCATGTGTGAAGAGCAGGGTGCTGCTGAGGGTTGTCTGTGCCATGCTATATGTCTTTCTCAT GAGTCAGTGGTCACCCTGAATGCATGTTTCCATTCAGGGATGGCCTACTGAGGGTGCGTGGCATCTTCTT CCCAGTGCCCCTGTGTTCATCCCTTCATTCTCATACCATCATCTCTATTGTGACCCCCACACGGCACCAG CCTTGATGGTGCTACCCTTTTGCTCCATCTATCCCTGTCTTGTTTGGGTTAGAAGCTGCGGTCTAATAAA CAGCCACACCACCCACCACTCAGAGTACTTGTGCAGCAACCCACTGCCCTGGGGACTCTCCCATGAGCTT TGCCTTCTTGGCTGAGTCTGCTCGCCTTGGATTTCATCCCCAGTTTATTCTTACTTCCCATTCACTCATT GCACATTCACAGGGCAGGTGCACACACTCTCATGTTTCCACCAACATGAACACACATAGATATATGCATG CTCATAGGTATGCACAGGCACACACTTGCTCACAGGGACATAGATATAGTGTGTCCACATATGTACTTAT ACCCATATACATACCTATAAACCATAGGTGCACACAAACTCACTCCTCTCTTGCTGCACACAGGTACACA CATGAAGGCACATGGACCCATCCATAAGCACTCACCAATACATAGACATGCATACACATATACTCTAGGC ATGAAGGGTCTTCAAAGTCTCCGAGGCCTTACAAGCTTAGGTGGTGGTGTTTCTCCCTCCCTGGGCCCTG ACCCCTCCCTGTGTTCTGTAGACCCTAAGGATGATGGACAGGCACTGGATGGAAGTGCAGGGATACTTTG GATGAGCACAGAGTTTATTTCAGGAGTAGGGACAGGCAGGGTGGCTCAGTAGCAGATGCCATCTCCCTCT GACATGATCACAGACACGCTGACATTGGTGGGTTTACCCGACAGACGGTCGATGGTCTTCTGGGTGAAGT TCATGGGCAAGGCCTCGTGGCCCACCATGCAGGAGTACTGGTCACCCTGTTTCCAGAGTTCAGCTGATAC ACGCAACACGCTTGTCACCAGGTAGGTGGTGGCTCCCTCGCCTGGCTCCTTTAGGGGCTCAAACACTAGG TAGCTTTCTGGGGACAGCTCCTCATTTCCATGCAGCCATCGCACCAGCACTTCTTTAGGGTTGAAAGCTC GCACCAGGCATGTCAGGGACACGAGCTCATTCAGGGCCAGCTCCTCCGACGGCGGCGGTAGCAGGTGGAC CTGGGGTGGGAAGGTGTTCACTGGAAGGTAGAAAGAAGAGTTATGGCTCAGACAAGGAGAGCAAGACCCC TCTGCCCTTCCCTTCTGGGCAGTTCCTCAGATAGCTCCAATTTCCCTCTGTGATATAAGGACAGGAGCAG TTAGTTGAGCATCTGTATTATAGGAAGAAAGCAGGCATGTGAGCAGGGAACGTCATACAATGTCCCGGGT ATGCATCTGGGCTCACCTGTGATTTTGGCAATTGTGCCAGTTAAGGTGTCAGACTCAGGATGGGTAACTG TGCACTTGAATGATGCGCCACTGTTCCAGCGCTCAGCACAGCCAGGCAGGACGCTGGACACACTGTAGCA GCCGCAGGAATTCTGCACAGCTTTCTTCTGCACTGCATCCTTCCCAGTGGAGGGCTCCCAGGTGAAGACA GCTCCCTCAGGATTTCTCAGGCCATTCAGAGTACATGTGAGGCTGGCATCTGAACCCAGGAGCAGGTCCT CAAGAGCTGGCCGCTGCAGTGACAGGCTGGGATGGCAGGAAGGAGGACAAGGAGGACAAGGAGGAGGAGG ACCTGTAACAGAGAAGTCCTAGCAAATCAGTATATTCTCCTTTTCTCCTTTGCTGTCCCCTTTTCTGGAT GTTCTGAGGCCTCAGTTCCTTATGGCCTGTTTACGCTTCCCTTCCCCCACCCCCATGGGAGGTTTCTGAG GGTCCCTGTGAGGGTGTGCCTCAGAGGGATATATGGATCTAGATAAGGTAGAACTTATCCCACCCCCAGC TGACCCCCTAACGTTCTTTACCAGAGCACTTCACATCCAATTCTTGGACGGCGTTAGAGTCATGTTGCAC GGAACATTTCACGGATTCTCCTTCTGGGCACTCGACAGCTGGCAGGGTCAACTGGCTGCTCATGGTGTAC CCTCCCCCAGAGGCCAGGGCAGGTGGGAAGTTTACGGTGGTTATATCCTTCCCACTCTTTCCCCAGGTCA CATTCATCGTGCCGGAAGGGAAGTAATCGTGAATCAGGCAGCCGATTATCACTGGGTCACTTGACAGAGC TCGTGGGAGTGTCAGTGGGTAGATGGTGGGATTTCTCGCAGAC Vaximmutor IgG Mus musculus 16059 AF010213 10090 12 881411 914690 + immunoglobulin heavy chain (V7183 family) Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG) >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA ACAAGCACAGTGCAAATTTCTGTCACCCTG Vaximmutor Vaximmutor peb1A Campylobacter jejuni VO_0011045 112360246 2V25 CDD:183381 EnsemblGenomes-Gn:Cj0921c EnsemblGenomes-Tr:CAL35041 GOA:Q0P9X8 InterPro:IPR001638 InterPro:IPR018313 PDB:2V25 192222 ? aspartate/glutamate-binding ABC transporter protein 8.53 27458.45 390 bifunctional adhesin/ABC transporter aspartate/glutamate-binding protein; Reviewed >CAL35041.1 aspartate/glutamate-binding ABC transporter protein [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819] MVFRKSLLKLAVFALGACVAFSNANAAEGKLESIKSKGQLIVGVKNDVPHYALLDQATGEIKGFEVDVAK LLAKSILGDDKKIKLVAVNAKTRGPLLDNGSVDAVIATFTITPERKRIYNFSEPYYQDAIGLLVLKEKKY KSLADMKGANIGVAQAATTKKAIGEAAKKIGIDVKFSEFPDYPSIKAALDAKRVDAFSVDKSILLGYVDD KSEILPDSFEPQSYGIVTKKDDPAFAKYVDDFVKEHKNEIDALAKKWGL Protective antigen Chitosan-DNA vaccines were prepared by embedding pcDNA3.1(+)-cadF and pcDNA3.1(+)-peblA with chitosan respectively. The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 [Ref1038:Zheng et al., 2007]. PorA Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 905550 218562871 Cj1259 AL111168 YP_002344650 192222 1189120 1190394 + major outer membrane protein 4.49 42413 424 Original (2000) note: Cj1259, porA, major outer membrane protein (MOMP), len: 424 aa; 94.6% identical to TR:AAC82317 (EMBL:U96452) C. jejuni major outer membrane porin (424 aa), and 98.0% identity to MOMP_CAMJE major outer membrane protein (fragments) (399 aa). No hp match. Also simlar in part to Cj1021c (63 aa, 34.5% identity in 55 aa overlap)~Updated (2006) note: Pfam domain PF05538 Campylobacter major outer membrane protein identified within CDS. Further support given to product function. Characterised within Campylobacter jejuni, so putative not added to product function. Functional classification -Membranes, lipoproteins and porins~PMID:7543469, PMID:9163918 >NC_002163.1:1189120-1190394 Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 chromosome, complete genome CATGAAACTAGTTAAACTTAGTTTAGTTGCAGCTCTTGCTGCAGGTGCTTTTTCAGCAGCTAACGCTACT CCACTTGAAGAAGCGATCAAAGATGTTGATGTATCAGGTGTATTAAGATACAGATACGATACAGGTAATT TTGATAAAAATTTCGTTAACAACTCAAATTTAAACAACAGCAAACAAGATCACAAATATAGAGCACAAGT TAACTTCAGTGCTGCTATAGCTGATAACTTCAAAGCTTTTGTTCAATTTGACTATAATGCTGCTGATGGT GGTTATGGTGCTAATGGAATAAAAAATGATCAAAAAGGACTTTTTGTTCGTCAATTATACTTAACTTATA CAAATGAAGATGTTGCTACAAGTGTAATCGCTGGTAAACAACAATTAAACCTTATCTGGACGGATAACGC TATTGATGGTTTAGTTGGCACAGGTGTTAAAGTAGTAAATAACAGCATCGATGGTTTAACTCTAGCTGCT TTTGCTGTAGATAGCTTCATGGCTGCAGAGCAAGGTGCAGATTTATTAGAACATAGTAATATTTCAACAA CATCAAATCAAGCTCCTTTTAAAGTAGATTCAGTAGGAAATCTTTACGGTGCTGCTGCTGTAGGTTCTTA TGATCTTGCTGGTGGACAATTCAACCCACAATTATGGTTAGCTTATTGGGATCAAGTAGCATTCTTCTAT GCTGTAGATGCAGCTTATAGTACAACTATCTTTGATGGAATCAACTGGACACTTGAAGGTGCTTACTTAG GAAATAGCCTTGATAGCGAACTTGATGATAAAACACACGCTAATGGCAATTTATTTGCTTTAAAAGGTAG CATTGAAGTAAATGGTTGGGATGCTAGCCTTGGTGGTTTATACTACGGTGATAAAGAAAAAGCTTCTACA GTTGTAATCGAAGATCAAGGTAATCTTGGTTCTTTACTTGCAGGTGAGGAAATTTTCTATACTACTGGTT CAAGACTAAATGGTGATACTGGTAGAAATATCTTCGGTTATGTAACTGGTGGATATACTTTCAACGAAAC AGTTCGCGTTGGTGCTGACTTCGTATATGGTGGAACAAAAACAGAAGCTGCTAATCATTTAGGTGGTGGT AAAAAACTTGAAGCTGTTGCAAGAGTAGATTACAAATACTCTCCAAAACTTAACTTCTCAGCATTCTATT CTTATGTGAACCTAGATCAAGGTGTAAACACTAATGAAAGTGCTGATCATAGCACTGTAAGACTTCAAGC TCTTTACAAATTCTA >YP_002344650.1 major outer membrane protein [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819] MKLVKLSLVAALAAGAFSAANATPLEEAIKDVDVSGVLRYRYDTGNFDKNFVNNSNLNNSKQDHKYRAQV NFSAAIADNFKAFVQFDYNAADGGYGANGIKNDQKGLFVRQLYLTYTNEDVATSVIAGKQQLNLIWTDNA IDGLVGTGVKVVNNSIDGLTLAAFAVDSFMAAEQGADLLEHSNISTTSNQAPFKVDSVGNLYGAAAVGSY DLAGGQFNPQLWLAYWDQVAFFYAVDAAYSTTIFDGINWTLEGAYLGNSLDSELDDKTHANGNLFALKGS IEVNGWDASLGGLYYGDKEKASTVVIEDQGNLGSLLAGEEIFYTTGSRLNGDTGRNIFGYVTGGYTFNET VRVGADFVYGGTKTEAANHLGGGKKLEAVARVDYKYSPKLNFSAFYSYVNLDQGVNTNESADHSTVRLQA LYKF Protective antigen Adult BALB/c mice were orally immunized with a recombinant glutathione S-transferase (GST) fused to PorA prepared from Campylobacter jejuni C31 (O:6,7) (GST-PorA) combined with a modified heat-labile enterotoxin of Escherichia coli as an adjuvant and later orally challenged with C31 strain or three heterologous strains: 48 (O:19), 75 (O:3), and 111 (O:1,44). The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline. Thus, PorA provided appreciable protection against colonization with heterologous serotypes[Ref1640:Islam et al., 2010] Abimiku et al., 1989 journal Abimiku AG, Dolby JM, Borriello SP 1989 Apr 102 2 271-80 Epidemiology and infection Abulreesh et al., 2006 journal Abulreesh HH, Paget TA, Goulder R 2006 Dec 1 40 23 7122-31 Environmental science & technology Andrews, 1998 journal Andrews GP 1998 Sep-Oct 11 5 305-8 Clinical laboratory science : journal of the American Society for Medical Technology Baqar et al., 1995a journal Baqar S, Bourgeois AL, Schultheiss PJ, Walker RI, Rollins DM, Haberberger RL, Pavlovskis OR 1995 Jan 13 1 22-8 Vaccine Baqar et al., 1995b journal Baqar S, Applebee LA, Bourgeois AL 1995 Sep 63 9 3731-5 Infection and immunity Baqar et al., 2008 journal Baqar S, Applebee LA, Gilliland TC Jr, Lee LH, Porter CK, Guerry P 2008 76 7 3170-3175 Infection and immunity Buckley et al., 2010 journal Buckley AM, Wang J, Hudson DL, Grant AJ, Jones MA, Maskell DJ, Stevens MP 2010 28 4 1094-1105 Vaccine Burr et al., 2005 journal Burr DH, Rollins D, Lee LH, Pattarini DL, Walz SS, Tian JH, Pace JL, Bourgeois AL, Walker RI 2005 Jul 29 23 34 4315-21 Vaccine Chintoan-Uta et al., 2015 journal Chintoan-Uta C, Cassady-Cain RL, Al-Haideri H, Watson E, Kelly DJ, Smith DG, Sparks NH, Kaiser P, Stevens MP 2015 33 46 6206-6211 Vaccine Dolby et al., 1986 journal Dolby JM, Newell DG 1986 Apr 96 2 143-51 The Journal of hygiene Engberg, 2006 journal Engberg J 2006 Nov 53 4 361-89 Danish medical bulletin Heimesaat et al., 2014 journal Heimesaat MM, Alutis M, Grundmann U, Fischer A, Tegtmeyer N, Böhm M, Kühl AA, Göbel UB, Backert S, Bereswill S 2014 4 77 Frontiers in cellular and infection microbiology Huang et al., 2007 journal Huang S, Sahin O, Zhang Q 2007 Jul 272 2 137-43 FEMS microbiology letters Huang et al., 2007 journal Huang S, Sahin O, Zhang Q 2007 272 2 137-143 FEMS microbiology letters Islam et al., 2010 journal Islam A, Raghupathy R, Albert MJ 2010 17 11 1666-1671 Clinical and vaccine immunology : CVI Islam et al., 2010 journal Islam A, Raghupathy R, Albert MJ 2010 17 11 1666-1671 Clinical and vaccine immunology : CVI Jagusztyn-Krynicka et al., 2004 journal Jagusztyn-Krynicka EK, Wyszynska A, Raczko A 2004 53 Suppl 7-15 Polish journal of microbiology / Polskie Towarzystwo Mikrobiologow = The Polish Society of Microbiologists Khoury et al., 1995 journal Khoury CA, Meinersmann RJ 1995 Oct-Dec 39 4 812-20 Avian diseases Kopecko, 1997 journal Kopecko DJ 1997 Dec 176 Suppl 2 S189-91 The Journal of infectious diseases Lee et al., 1999 journal Lee LH, Burg E 3rd, Baqar S, Bourgeois AL, Burr DH, Ewing CP, Trust TJ, Guerry P 1999 Nov 67 11 5799-805 Infection and immunity Martin et al., 1999 journal Martin PR, Mulks MH 1999 Aug 15 25 3 245-54 FEMS immunology and medical microbiology Nelson et al., 2007 journal Nelson JM, Chiller TM, Powers JH, Angulo FJ 2007 Apr 1 44 7 977-80 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Pawelec et al., 1997 journal Pawelec D, Rozynek E, Popowski J, Jagusztyn-Krynicka EK 1997 Oct 19 2 137-50 FEMS immunology and medical microbiology Pawelec et al., 2000 journal Pawelec DP, Korsak D, Wyszynska AK, Rozynek E, Popowski J, Jagusztyn-Krynicka EK 2000 Apr 1 185 1 43-9 FEMS microbiology letters Prokhorova et al., 2006 journal Prokhorova TA, Nielsen PN, Petersen J, Kofoed T, Crawford JS, Morsczeck C, Boysen A, Schrotz-King P 2006 Sep 29 24 40-41 6446-55 Vaccine Rice et al., 1997 journal Rice BE, Rollins DM, Mallinson ET, Carr L, Joseph SW 1997 Dec 15 17-18 1922-32 Vaccine Scott, 1997 journal Scott DA 1997 Dec 176 Suppl 2 S183-8 The Journal of infectious diseases Sizemore et al., 2006 journal Sizemore DR, Warner B, Lawrence J, Jones A, Killeen KP 2006 May 1 24 18 3793-803 Vaccine Smibert, 1978 journal Smibert RM 1978 32 673-709 Annual review of microbiology Theoret et al., 2012 journal Theoret JR, Cooper KK, Zekarias B, Roland KL, Law BF, Curtiss R 3rd, Joens LA 2012 19 9 1426-1431 Clinical and vaccine immunology : CVI Walker, 2005 journal Walker RI 2005 May 16 23 26 3369-85 Vaccine Wallis, 2004 journal Wallis TS 2004 119 343-50 Developments in biologicals White et al., 1997 journal White PL, Baker AR, James WO 1997 Aug 16 2 525-41 Revue scientifique et technique (International Office of Epizootics) Wilkinson et al., 2003 journal Wilkinson J, Rood D, Minior D, Guillard K, Darre M, Silbart LK 2003 Oct 82 10 1565-72 Poultry science Wyszynska et al., 2004 journal Wyszynska A, Raczko A, Lis M, Jagusztyn-Krynicka EK 2004 Mar 29 22 11-12 1379-89 Vaccine Yeh et al., 2015 journal Yeh HY, Hiett KL, Line JE 2015 197 2 353-358 Archives of microbiology Zeng et al., 2009 journal Zeng X, Xu F, Lin J 2009 77 12 5437-5448 Infection and immunity Zheng et al., 2007 journal Zheng H, Cai FC, Zhong M, Deng B, Li X, Zhang XP 2007 41 5 375-379 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]