Streptococcus pneumoniae 1313 S. pneumoniae is normally found in the nasopharynx. It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. It can cause otitis media or sinusitis if it enters areas such as the Eustachian tube or nasal sinuses. Pneumonia occurs if the organisms are inhaled into the lungs and not eliminated. S. pneumoniae can activate complement, stimulate cytokine production, and attracts neutrophils and other white blood cells. The organism's polysaccharide capsule makes it resistant to phagocytosis. S. pneumoniae can spread to other areas and cause various diseases. S. pneumoniae has several virulence factors, including the polysaccharide capsule, pneumococcal surface proteins, and IgA1 protease (Wiki: S. pneumoniae). Pneumonia The bacteria invade and grow primarily due to their resistance to the host phagocytic response. The cell wall components directly activate multiple inflammatory cascades, including the alternative pathway of complement activation, the coagulation cascade and the cytokine cascade, inducing interleukin-1, interleukin-6 and tumor necrosis factor (TNF) from macrophages and other cells (Textbook of Bacteriology). Pneumococci spontaneously cause disease in humans, monkeys, rabbits, horses, mice and guinea pigs. Nasopharyngeal colonization occurs in approximately 40% of the population (Textbook of Bacteriology). Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus aerotolerant anaerobe and a member of the genus Streptococcus. S. pneumoniae is the most common cause of both pneumonia overall and fatal pneumonia. Antibiotic resistance has developed worldwide and is most frequent in pneumococcal serotypes that are most prevalent in children (types/groups 6, 14, 19, and 23). The incidence of pneumococcal disease is the highest in children < 2 years of age and in adults > 65 years of age. Other important risk factors are chronic heart and lung disease, cigarette smoking, and asplenia (Ortqvist et al., 2005). Other than pneumonia, it also causes acute sinusitis, otitis media, meningitis, bacteremia, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess. 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 DNA vaccine expressing PspA VO_0004516 DNA vaccine Research pSecTag2A [Ref2528:Ferreira et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol (Ferreira et al., 2006). Groups of at least six mice were inoculated intramuscularly with 50 μl of 10 μM cardiotoxin into each tibialis anterior muscle, 5 days before immunization with 50 μg vaccine vector in PBS (100 μl). Mice received a booster after 3 weeks with the same dose of plasmid DNA. For immunization with recombinant protein, mice were injected subcutaneously with 5 μg rPspA3NS, using aluminium hydroxide as the adjuvant, and also boosted 3 weeks after priming (Ferreira et al., 2006). VO_0000286 All the immunized groups showed significant protection when compared with control groups. Animals immunized with pSec-pspA3NS showed a tendency towards increased survival when compared with animals primed with rPspA3NS (Ferreira et al., 2006). Immunized mice were challenged by intraperitoneal injection of 200 c.f.u. S. pneumoniae strain St 679/99 (PspA clade 3, serotype 6B) in 0·5 ml saline 6 weeks after priming. Animals were then observed for 2 weeks (Ferreira et al., 2006). licensed Pneumococcal disease human vaccine Generic Unknown VO_0000675 Conjugate vaccine Licensed A generic representation of vaccines utilized to prevent pneumococcal disease (including pneumonia) in humans, most commonly formulated as conjugate vaccines where bacterial polysaccharides are chemically linked to a protein carrier to enhance immunogenicity. These vaccines are widely used for both children and adults to protect against Streptococcus pneumoniae infections. Pneumo 23 Pneumococcal Polysaccharide Vaccine Pneumo 23 Sanofi Pasteur Ltd VO_0010731 Subunit vaccine Licensed Intramuscular injection (i.m.), Subcutaneous injection Canada Products: Polysaccharide. Store at 2° to 8°C (35° to 46°F). Intramuscular injection (i.m.), Subcutaneous injection pneumococcal polysaccharide conjugate vaccine serotype 1 (PNC-1) VO_0004265 Conjugate vaccine Research intranasal immunization intranasal immunization Administration of PNC-1 i.n. with either LT-K63 or LT-R72 elicited significantly higher antibody responses than the s.c. route for both 0.5- and 2.0-μg doses of PNC-1 in saline (Jakobsen et al., 1999). NMRI Mice were immunized i.n. with 0.5 or 2.0 μg of PNC-1 alone or mixed with either LT-K63 or LT-R72 (Jakobsen et al., 1999). Immunization i.n. with PNC-1 and LT-K63 or LT-R72 conferred 100% clearance of lung infection caused by serotype 1 pneumococci (Jakobsen et al., 1999). Mice were challenged with 50 μl of pneumococcal suspension i.n. and were allowed to aspirate it into the lungs for 10 min (Jakobsen et al., 1999). Pneumovax 23 Pneumococcal Vaccine, Polyvalent Pneumovax 23 Merck & Co, Inc. VO_0000088 Subunit vaccine Licensed USA (License #0002) Pneumococcal polysaccharide vaccine provides at least 85% protection in those under 55 years of age for five years or longer. Immunization is suggested for those at highest risk of infection, including those 65 years or older. The vaccine is generally given with a single lifetime dose (Wiki: S. pneumoniae). The most common adverse experiences reported with PNEUMOVAX 23 in clinical trials were: Local reaction at injection site including soreness, erythema, warmth, swelling and induration, and fever <102°F. In post-marketing experience, injection site cellulitis-like reactions were reported rarely; between 1989 and 2002, when approximately 43 million doses were distributed, the annual reporting rate was <2/100,000 doses (Merck: PNEUMOVAX 23). Store unopened and opened vials at 2-8°C (36-46°F). It consists of a mixture of highly purified capsular polysaccharides from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae, including the six serotypes that most frequently cause invasive drug-resistant pneumococcal infections among children and adults in the United States (FDA: PNEUMOVAX 23). It has been established that the purified pneumococcal capsular polysaccharides induce antibody production and that such antibody is effective in preventing pneumococcal disease (Merck: PNEUMOVAX 23). In many clinical studies on the efficacy of the vaccine, it has been found to have a 70-90% efficacy rate (FDA: PNEUMOVAX 23). Side effects of vaccination include: redness and soreness of the injection site, fever, and chills (Merck: PNEUMOVAX 23). Prevnar Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein) Prevnar Wyeth Pharmaceuticals Inc. VO_0000090 Conjugate vaccine Licensed USA (License #0003) In the USA, a heptavalent pneumococcal conjugate vaccine vaccine (PCV 7) (e.g. Prevnar) is recommended since 2000 for all children aged 2–23 months and for at-risk children aged 24–59 months. The normally 4-doses series is given at 2, 4, 6 & 12–14 months of age. Protection is good against deep pneumococcal infections (especially septicemia and meningitis) (Wiki: S. pneumoniae). DO NOT FREEZE. Store refrigerated at 2°C TO 8°C. Each serotype is grown in soy peptone broth. The individual polysaccharides are purified through centrifugation, precipitation, ultrafiltration, and column chromatography. A sterile solution of saccharides of the capsular antigens of Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein (FDA: Prevnar). There were no reports of streptococcus pneumoniae in the group vaccinated with PREVNAR whereas in the control group, there were between 17-22 cases reported after vaccination (FDA: Prevnar). Efficacy was assessed in a randomized, double-blinded clinical trial in a multiethnic population at Northern California Kaiser Permanente (NCKP) from October 1995 through August 20, 1998, in which 37,816 infants were randomized to receive either Prevnar or a control vaccine at 2, 4, 6, and 12-15 months of age (FDA: Prevnar). Side effects of vaccination include: fever, irratibility, drowsiness, decreased appetite, rash and soreness/redness of the injection site. Prevnar 13 Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein] Prevnar Wyeth Pharmaceuticals, Inc VO_0001244 Conjugate vaccine Licensed Intramuscular injection (i.m.) USA, Canada Aluminum phosphate Store refrigerated at +2ºC to +8ºC (36ºF to 46ºF) Intramuscular injection (i.m.) PsaA DNA Vaccine VO_0004517 DNA vaccine Licensed pCI [Ref2529:Miyaji et al., 2001] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Analysis of sera from mice immunized with purified PsaA showed the induction of mostly IgG1, that is, a Th2 like response. Furthermore, mice immunized with pCI-psaA developed readily detectable serum antibody titers 1 month after priming (Miyaji et al., 2001). Five male BALB/c mice were inoculated into each muscle tibialis anterior as previously described with 100 μl of 10 μM cardiotoxin and after 5 days with 25 μg of plasmid DNA in PBS (50 μl) (Miyaji et al., 2001). VO_0000286 Immunization of mice with purified PsaA was shown to be protective against challenge with an heterologous S. pneumoniae strain (Miyaji et al., 2001). S. pneumoniae 6PGD Protein Vaccine VO_0004069 Subunit vaccine Research Intraperitoneal injection (i.p.) Inject Alum adjuvant (Daniely et al., 2006). Intraperitoneal injection (i.p.) Recombinant 6-Phosphogluconate dehydrogenase (6PGD) (Daniely et al., 2006). Recombinant protein preparation BALB/c Six-week-old BALB/c female mice were immunized intraperitoneally with 25 µg of r6PGD and 75 µl of Inject Alum adjuvant on days 0 (primary immunization) and 21 (booster). Control mice were sham-immunized with adjuvant only (Daniely et al., 2006). Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge (Daniely et al., 2006). For respiratory challenge r6PGD immunized and control mice were anaesthetized with pentobarbital sodium (0·6 mg/kg) and inoculated intranasally with 1 × 10^8 S. pneumoniae strain WU2 (in 25 µl PBS). This inoculum's size was used as it was found to be the lowest that causes 100% mortality in our mouse model system within 96 h. Survival was monitored daily (Daniely et al., 2006). S. pneumoniae CbpA Protein Vaccine VO_0004005 Subunit vaccine Research Intraperitoneal injection (i.p.) Monophospholipid A (MPL) and aluminium phosphate (AlPO4) (Ogunniyi et al., 2001). Intraperitoneal injection (i.p.) N-terminal fragment of choline binding protein A (CbpA) (Ogunniyi et al., 2001). Recombinant protein preparation BALB/c 5- to 6-week-old male BALB/c mice (13 to 15 per group) were immunized intraperitoneally with either adjuvant alone, adjuvant plus CbpA, or CbpA alone. Each mouse received three doses of 10 μg of each protein antigen in either formulation (AlPO4 or MPL plus AlPO4) at 12- to 14-day intervals (Ogunniyi et al., 2001). CbpA was able to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 (Ogunniyi et al., 2001). Intraperitoneal-challenge experiments were carried out 2 weeks after the third immunization using a highly virulent capsular type 2 strain (D39). Groups of immunized BALB/c mice were infected with either 1.3 × 10^5 or 1.3 × 10^7 CFU of the challenge strain. The challenge dose was equivalent to approximately 10^3 or 10^5 times the 50% lethal dose (LD50), respectively, for BALB/c mice. The mice were closely monitored for 21 days, and the survival time of each mouse was recorded (Ogunniyi et al., 2001). S. pneumoniae ClpP protein Vaccine VO_0004006 Subunit vaccine Research Intraperitoneal injection (i.p.) Aluminum hydroxide Intraperitoneal injection (i.p.) ATP-dependent caseinolytic protease (ClpP) Recombinant protein preparation BALB/c Female BALB/c mice, weighing 16 to 18 g, were immunized three times at 14-day intervals with 10 µg of protein in alum adjuvant (3:1 [vol/vol]) of either ClpP protein in alum adjuvant or control protein in alum. Mice were boosted intraperitoneally with the same doses on days 14 and 28 (Wu et al., 2010). Compared to the control protein, ClpP reduced the median bacterial load nearly 100-fold in the focal pneumonia model (Wu et al., 2010). For the intraperitoneal challenge models, at 2 weeks after the last immunization BALB/c mice were administrated the virulent pneumococcal strain D39 at 1,500 times the 50% lethal dose (LD50; 1.5 x 10^5 CFU) or 150 times the LD50 (2.0 x 10^4 CFU). In the focal pneumonia models, BALB/c mice were intranasally inoculated with pneumococcal strain 31614 (serotype 14, 1.5 x 10^6 CFU) or 31693 (serotype 19F, 10^7 CFU). For intranasal challenge with pneumococcal strain D39, mice inspired the virulent pneumococcal strain D39 at 104 (7.5 x 10^7 CFU) or 103 (6.0 x 10^6 CFU) times the LD50 in a volume of 40 µl under injection anesthesia (Wu et al., 2010). S. pneumoniae detoxified PlyD1 Protein Vaccine Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Recombinant PLY was produced from Escherichia coli containing the entire gene sequence of wild-type pneumolysin from strain R36A; the protein was column purified. PlyD1, a highly detoxified PLY variant, was generated by site-directed mutagenesis and differs from the wild-type form by three amino acid substitutions of T65C, G293C, and C428A. Recombinant PlyD1 protein was expressed in E. coli as soluble protein and column purified.(Salha et al., 2012) Intramuscular injection (i.m.) Recombinant protein preparation S. pneumoniae DnaJ Protein Vaccine Recombinant vector vaccine Research Intramuscular injection (i.m.) PCR amplified DnaJ was ligated in pQE-30 expression vector and subsequently transformed in E. coli DH5alpha strain.(Khan et al., 2006) Intramuscular injection (i.m.) Recombinant protein preparation PCR amplified DnaJ was ligated in pQE-30 expression vector and subsequently transformed in E. coli DH5alpha strain.(Khan et al., 2006) S. pneumoniae GtS Protein Vaccine VO_0004068 Subunit vaccine Research Intraperitoneal injection (i.p.) Imject Alum adjuvant (Mizrachi et al., 2007). Intraperitoneal injection (i.p.) recombinant (r) Glutamyl tRNA synthetase (GtS) (Mizrachi et al., 2007). Recombinant protein preparation BALB/c OlaHsd Mice were immunized intraperitoneally with 25 μg of rGtS and 75 μL of Imject Alum adjuvant on days 0 and 21. Control mice were sham immunized with adjuvant only (Mizrachi et al., 2007). Thirty-nine percent of rGtS-immunized mice survived a lethal bacterial challenge, whereas no control mice survived (Mizrachi et al., 2007). For lethal respiratory challenge with S. pneumoniae, rGtS‐immunized and control mice were anesthetized with isoflurane and inoculated intranasally with S. pneumoniae serotype 3 strain WU2 (in 25 μL of PBS). The size of this inoculum was found to be the lowest that causes 100% mortality in control mice within 96 h. Survival was monitored daily (Mizrachi et al., 2007). S. pneumoniae PhpA-79 Protein Vaccine VO_0004063 Subunit vaccine Research subcutaneous injection 100 μg of monophosphoryl lipid A (MPL; Corixa, Hamilton, Mont.) per dose (Zhang et al., 2001). subcutaneous injection Recombinant PhpA-79 Recombinant protein preparation CBA/N CBA/N mice, at 10 animals per group, were immunized with 5 μg of either rPhpA-79 or rPhpA-20. For parenteral immunization, rPhpA-79 or rPhpA-20 protein was mixed with 100 μg of monophosphoryl lipid A (MPL; Corixa, Hamilton, Mont.) per dose to a final volume of 200 μl in saline and then injected s.c. into mice. All groups received a booster with the same dose and by the same route 3 and 5 weeks after the primary immunization. Control mice were injected with MPL alone (Zhang et al., 2001). Immunization with either rPhpA-79–MPL provided 100% protection against death caused by type 3 S. pneumoniae infection (Zhang et al., 2001). Mice were challenged with either serotype 3 or serotype 14 streptomycin-resistant S. pneumoniae (Zhang et al., 2001). S. pneumoniae PiaA Protein Vaccine VO_0004070 Subunit vaccine Research Intraperitoneal injection (i.p.) Imject Alum No. 77161 Intraperitoneal injection (i.p.) Recombinant PiaA protein (Brown et al., 2001). Recombinant protein preparation BALB/c For the active protection experiments, each mouse was immunized by intraperitoneal (i.p.) injection of 100 μl of each protein preparation in alum adjuvant on days 0, 10, and 20 (Brown et al., 2001). After 14 days the mortality of the group of mice immunized PiuA was 52%, showing that immunization with these proteins protects against systemic infection with S. pneumoniae (Brown et al., 2001). On day 34 mice were challenged i.p. with ca. 10^6 CFU of S. pneumoniae strain D39 organisms (Brown et al., 2001). S. pneumoniae PspA Protein Vaccine VO_0004007 Subunit vaccine Research Intraperitoneal injection (i.p.) Alum Intraperitoneal injection (i.p.) Recombinant protein preparation BALB/c and CD1 The mice received three doses of 10 μg of each antigen alone (or in combination) in 100 μg of alum adjuvant via Intraperitoneal injection (i.p.) at 14-day intervals or a placebo (Ogunniyi et al., 2007). PspA elicited protection by using moderate challenge doses of S. pneumoniae (Ogunniyi et al., 2007). Mice were challenged i.p. 2 weeks after the third immunization with either the highly virulent capsular type 2 strain D39 or a serotype 6A (WCH16) strain (Ogunniyi et al., 2007). S. pneumoniae pspA-rBCG Vector Vaccine VO_0004601 Recombinant vector vaccine Research recombinant Bacille Calmette-Guerin (rBCG) [Ref2795:Langermann et al., 1994] Intramuscular injection (i.m.) Streptococcus pneumoniae is one of the leading causes of bacterial pneumonia and acute otitis media, a type of meningitis. It is becoming increasingly antibiotic resistant and the current available vaccine does not elicit protection in children. (Langermann et al., 1994) Intramuscular injection (i.m.) Pneumococcal surface protein A (PspA) present on all strains of pneumococci (Langermann et al., 1994) Recombinant protein preparation BALB/c and C3H/HeJ mice A single intraperitoneal inoculation with a live BCG bacterial vaccine expressing PspA as a secreted mature protein in or a chimeric exported lipoprotein (rBCG-PspA), followed by a booster at 17 weeks(Langermann et al., 1994) VO_0003057 Mice experienced passive protection with the use of rBCG against lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular sero- types(Langermann et al., 1994) BALB/c and C3H/HeJ mice immunized with rBCG-PspA vaccine strains were challenged intraperitoneally with 10^4 CFU of the highly lethal S. pneumoniae strain WU2 (Langermann et al., 1994) S. pneumoniae RASV synthesizing PsaA VO_0004071 Recombinant vector vaccine Research Attenuated Salmonella enterica serovar Typhimurium strain RASV [Ref1202:Wang et al., 2010]. Intranasally Intranasally Recombinant vector construction BALB/c, C57BL/6J Mice were inoculated intranasally with 10 µl or orally with 20 µl of BSG containing 1 x 10^9 CFU of the RASV or control strain. In some experiments, the mice were boosted at week 6 with the same dose by using the same route as that used for primary immunization (Wang et al., 2010). BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains (Wang et al., 2010). At week 10, mice were challenged either by intraperitoneal injection with 2 x 10^4 CFU of S. pneumoniae WU2 (equal to 100x the 50% lethal dose [LD50]) or intranasally with 20 µl containing 5 x 10^6 CFU S. pneumoniae strain L82016 or E134 or 1 x 10^7 CFU of strain A66.1 or D39 (Wang et al., 2010). S. pneumoniae SrtA Protein Vaccine VO_0004008 Subunit vaccine Research Intraperitoneal injection (i.p.) Freund's adjuvant (Gianfaldoni et al., 2009). Intraperitoneal injection (i.p.) Recombinant sortase A (SrtA) (Gianfaldoni et al., 2009). Recombinant protein preparation BALB/c mice Specific-pathogen-free BALB/c mice (Charles River) received three intraperitoneal administrations, 2 weeks apart, of 20 μg of SrtA along with Freund's adjuvant. Controls received the same course of saline plus adjuvant (Gianfaldoni et al., 2009). Intraperitoneal immunization with recombinant SrtA was found to have conferred to mice protection against S. pneumoniae intraperitoneal challenge and the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA was observed, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen (Gianfaldoni et al., 2009). Three weeks after the last immunization, the animals were challenged intraperitoneally with one of the following S. pneumoniae strains: TIGR4, 1.4 × 10^2 CFU/mouse; D39, 10^3 CFU/mouse; or 35B-SME15, 7 × 10^3 CFU/mouse (Gianfaldoni et al., 2009). Synflorix Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed Synflorix GlaxoSmithKline Inc. VO_0001245 Conjugate vaccine Licensed Intramuscular injection (i.m.) Canada SYNFLORIXâ„¢ [(pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed] is a 10- valent pneumococcal polysaccharide conjugate vaccine using protein D derived from Non-Typeable Haemophilus influenzae as a carrier protein for 8 out of the 10 serotypes (1, 4, 5, 6B, 7F, 9V, 14 and 23F). Serotypes 18C and 19F are conjugated to tetanus toxoid and to diphtheria toxoid, respectively. All conjugates are adsorbed onto aluminum phosphate (GSK: Synflorix). Aluminum phosphate Store in a refrigerator (2°C - 8°C). Intramuscular injection (i.m.) Pneumococcal polysaccharides of serotypes 1,4,5,6B,7F,9V,14,18C,19F,23F (GSK: Synflorix). CbpA Streptococcus pneumoniae D39 VO_0011203 4441159 116515359 SPD_2017 CP000410 YP_817402 1W9R 373153 1995043 1997148 - choline binding protein A 8.27 75722.56 701 equivalent gene in S.pneumoniae R6 = spr1995 This gene is also called SpsA, pspC (pneumococcal surface protein C)and Hic; identified by match to protein family HMM PF01473; match to protein family HMM PF04650; match to protein family HMM PF05062; match to protein family HMM TIGR01168 >NC_008533.1:1995043-1997148 Streptococcus pneumoniae D39, complete genome TTTAGTTTACCCATTCACCATTGGCATTGACTCCATAGCCATCTACAGTTGTGTTGACTGCAAGGGCACC TGAGCCATTGACATAGTACCATTTATCTGATACTTTGAACCATTGGCTTGCTTTCATAGCACCTGATGCT TCAAGATAGTACCAGGTATCTCCATCTTTCACCCAACCTGTCGCCATATCACCATTAGCGTTGAGGTAAT ACCATGAACCGTTGTATTGGAGCCATCCTGTCGCCATATCACCATTAGCGTTGAGGTAGTACCATGAACC GTTGTTTTGGAGCCATCCTGTCGCCATATCACCATTAGCGTTGAGGTAGTACCATGAGCCATTGTATTGG AGCCATCCTGTCGCCATAGCGCCATTGCTGTTTAGGTAGTACCATGAACCATTGTATTGGAGCCATCCTG TCGCCATAGCACCATTAGCGTTTAGGTAGTACCATGAACCATTGTTTTGGAGCCATCCTGTTGCCATTGA ACCATTAGCGTTTAGATAGTACCATGAACCATTGTTTTGGAGCCATCCTGTCGCCATAGCACCATTAGCG TTTAGATAGTACCATGAACCGTTGTTTTGGAGCCATCCTGTTGCCATTGAACCATCAGTATTGTAGAAGT ACCACATACCGTTTTCTTGTTTCCAGCCTGTTTTTGGAGTAGATGGTTGTGCTGGTTTTTCAGTTTTTGG CGGTTGCTGTTGAGTCAAGCGATTATATTCTTCTTCTGATCTACGAGCATAGTCTTCTTCAGCTTGTTGA TCATCTGTTTTTTCTGCTTTTGGTTGTTCAGCTGGCTTCTCTGGTTTTGGAGCTGGTTTTTCTGGTTGAG TAGCCGGCGCTGGTTGTGGTTGTTCAGCTGGTTTTTCTTTAACTTTATCTTCTTCTGCTGCTTTTCGTTT AGCTTCTTCTTCTGCTTTTTTACGATCTGTCTTGATGTTTTCTAACCTTGTAGCCTCAGCTTTTTTACTC TCAACTTTCGCTTTTGCTTGCTTAATTTTTTCCTCGTCTCGAGGTTCCTTAGCTTCCTCTTTTACTAGTT CAAGCTCCGCTTCTTTAACTTTCACATCGGACTCAGCAATTTCAAGGTCAAGCGTTTTGTAAGTATTGGT TGGGTAGTTACGGCGATCTTCTTCTTTTTGATCCTTGGCTTTTTTCTCAGCTTCTTCAACCTTCTTCTCA GCTTCTGCTACCTTTTTTCCTGATTTCAGGGATGAGCTTGGAAGAGTTTCTTCACCTACGCTAGAATCTG AAGACTTCGCATCATTTTCTTTTTTATCAGGTGTTGCTAGCTCTCCAGGAACTCCTCGTTTTGCCCGCCC CTTTGGTTTACCTTGATCTGAAGTCGCTACATTAGCTTCCTTCAACTTAGCATCTGCTTTTCGTTTAGCT TCTTCTTCTGCTTTTTTACGATCTGTCTTGATGTTTTCTAACCTTGTAGCCTCAGCTTTTTTACTCTCAA CTTTCTCTTTTGCTTGCTTAATTGTGCCCTCGTTTCGAGATTCTTTAGCTTCCTCTTTTACTAGTTCAAG CTCCGCTTCTTTAACTTTCACATCGAACTCAGCAATTTCAAGTTCAAGCGTTTTGTAAGTATTGGTTGGG TAGTTACGACGATCTTCTTCTTTTTGATCCTCGGCTTTTTTCTTAGCTTCTTCAACCTTCTTCTTAGCTT CTGCTACCTTTTCTCCTGGTTTCAATGTATCTTTTTTAAACTTCTCAAAAGCTGCGTCTAACTTTGCTTT TATTTCTGACGGCAACTCATCTTTCGACTTCTCTTCTAAAACATTTAATTCACGCAAATACTTCGTTTTA ATTGCGCTCAACTTTATGTTTAAGGCGACATTTTGGGTATGTTTTCTTCTATCTAGTTGAATCTCCCTCA ACATTTTTTCTATATATTCATCGACGACTTGTTTAGCAGCTTTCCTATGTTCTGTCTTTGCCATATTAGA AGAAGTGGCTGCTTGGGTACTTCCCTCGTTCTCTGTCGCATGAACCACACTTCCCATAACAAGACTGGCA ACAGCTACACTAGCTACTCCAATACTAAATTTACGAATTGAATAATGTACTTTTCTTTCGCTTTTTGATG CAAACA >YP_817402.1 choline binding protein A [Streptococcus pneumoniae D39] MFASKSERKVHYSIRKFSIGVASVAVASLVMGSVVHATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIE KMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK VAEAKKKVEEAKKKAEDQKEEDRRNYPTNTYKTLELEIAEFDVKVKEAELELVKEEAKESRNEGTIKQAK EKVESKKAEATRLENIKTDRKKAEEEAKRKADAKLKEANVATSDQGKPKGRAKRGVPGELATPDKKENDA KSSDSSVGEETLPSSSLKSGKKVAEAEKKVEEAEKKAKDQKEEDRRNYPTNTYKTLDLEIAESDVKVKEA ELELVKEEAKEPRDEEKIKQAKAKVESKKAEATRLENIKTDRKKAEEEAKRKAAEEDKVKEKPAEQPQPA PATQPEKPAPKPEKPAEQPKAEKTDDQQAEEDYARRSEEEYNRLTQQQPPKTEKPAQPSTPKTGWKQENG MWYFYNTDGSMATGWLQNNGSWYYLNANGAMATGWLQNNGSWYYLNANGSMATGWLQNNGSWYYLNANGA MATGWLQYNGSWYYLNSNGAMATGWLQYNGSWYYLNANGDMATGWLQNNGSWYYLNANGDMATGWLQYNG SWYYLNANGDMATGWVKDGDTWYYLEASGAMKASQWFKVSDKWYYVNGSGALAVNTTVDGYGVNANGEWV N Protective antigen Mice were actively immunized with a fragment of choline binding protein A (CbpA; also known as PspC, Hic, and SpsA). CbpA was able to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 [Ref1274:Ogunniyi et al., 2001]. ClpP Streptococcus pneumoniae D39 VO_0011193 4441476 WP_000613477 SPD_0650 CP000410 YP_816144 1Y7O CDD:178955 CDD:132928 1301 668966 669556 + ATP-dependent Clp protease proteolytic subunit 4.37 22213.63 293 ATP-dependent Clp protease proteolytic subunit; Reviewed; PRK00277 >NC_008533.1:668966-669556 Streptococcus pneumoniae D39, complete genome AATGATTCCTGTAGTTATTGAACAAACAAGCCGTGGAGAACGTTCTTACGATATTTACTCACGTCTTCTC AAAGACCGCATCATTATGCTGACAGGTCCGGTTGAAGACAATATGGCTAACTCTGTTATTGCCCAACTGC TTTTCTTGGATGCCCAAGATAGTACAAAAGATATTTACCTTTATGTCAATACACCAGGTGGTTCTGTTTC AGCTGGTTTGGCAATCGTAGATACCATGAACTTTATCAAGGCAGATGTCCAAACCATTGTTATGGGAATG GCTGCATCTATGGGAACAGTCATCGCATCAAGTGGAGCAAAAGGCAAACGTTTCATGCTTCCAAATGCTG AATACATGATTCACCAACCAATGGGCGGTACAGGTGGTGGTACCCAACAAACTGATATGGCTATCGCTGC AGAACACTTGCTCAAAACTCGTAATACCTTGGAAAAAATCTTGGCTGAAAATTCAGGTCAGTCAATGGAA AAAGTCCATGCAGATGCAGAACGTGATAACTGGATGAGCGCCCAGGAAACACTTGAATATGGCTTTATTG ATGAAATTATGGCCAACAATTCATTGAACTA >WP_000613477.1 MULTISPECIES: ATP-dependent Clp protease proteolytic subunit [Streptococcus] MIPVVIEQTSRGERSYDIYSRLLKDRIIMLTGPVEDNMANSVIAQLLFLDAQDSTKDIYLYVNTPGGSVS AGLAIVDTMNFIKADVQTIVMGMAASMGTVIASSGAKGKRFMLPNAEYMIHQPMGGTGGGTQQTDMAIAA EHLLKTRNTLEKILAENSGQSMEKVHADAERDNWMSAQETLEYGFIDEIMANNSLN Protective antigen The protective effects of ATP-dependent caseinolytic protease (ClpP) was evaluated. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), clpP elicited some protection in mice [Ref1203:Wu et al., 2010]. DnaJ WP_001035362 CDD:331332 CDD:227588 CDD:332379 1313 ? hypothetical protein 4.54 79758.9 820 Gap junction protein N-terminal region; cl26511 >WP_001035362.1 hypothetical protein [Streptococcus pneumoniae] MNKKKMILTSLASVAILGAGFVTSQPTFVRAEESPQVVEKSSLEKKYEEAKAKADTAKKDYETAKKKAED AQKKYEDDQKRTEEKARKEAEASQKLNDVALVVQNAYKEYREVQNQRSKYKSDAEYQKKLTEVDSKIEKA RKEQQDLQNKFNEVRAVVVPEPNALAETKKKAEEAKAEEKVAKRKYDYATLKVALAKKEVEAKELEIEKL QYEISTLEQEVATAQHQVDNLKKLLAGADPDDGTEVIEAKLKKGEAELNAKQAELAKKQTELEKLLDSLD PEGKTQDELDKEAEEAELDKKADELQNKVADLEKEISNLEILLGGADPEDDTAALQNKLAAKKAELAKKQ TELEKLLDSLDPEGKTQDELDKEAEEAELDKKADELQNKVADLEKEISNLEILLGGADSEDDTAALQNKL ATKKAELEKTQKELDAALNELGPDGDEEETPAPAPQPEQPAPAPKPEQPAPAPKPEQPAPAPKPEQPAPA PKPEQPAPAPKPEQPAKPEKPAEEPTQPEKPATPKTGWKQENGMWYFYNTDGSMAIGWLQNNGSWYYLNA NGAMATGWVKDGDTWYYLEASGAMKASQWFKVSDKWYYVNSNGAMATGWLQYNGSWYYLNANGDMATGWL QYNGSWYYLNANGDMATGWAKVNGSWYYLNANGAMATGWAKVNGSWYYLNANGSMATGWVKDGDTWYYLE ASGAMKASQWFKVSDKWYYVNGLGALAVNTTVDGYKVNANGEWV Protective antigen All the control mice died within 2 days of post-infection, while 70% of animals immunized with DnaJ survived the lethal challenge by S. pneumoniae. The study reveals that immunization of mice with DnaJ elicits protective immunity against S. pneumoniae infection.[Ref5091:Khan et al., 2006] GltX Streptococcus pneumoniae TIGR4 VO_0011201 931970 WP_000031087 SP_2069 AE005672 NP_346492 CDD:234953 1313 1976626 1978086 - glutamate--tRNA ligase 4.67 54587.89 560 glutamyl-tRNA synthetase; Reviewed; PRK01406 >NC_003028.3:1976626-1978086 Streptococcus pneumoniae TIGR4, complete genome TTTATTTAGAGATTTCTTTTAGCATGTTTTCGATATGCTGAATTGATTTTTCACGTCCAAGCAAGAAAAT TGTATCTGGTAATTCTGGCCCATGCATTTCGCCTGAAACTGCGATACGAATAGGCATGAAAAGATTTTTC CCTTTAATACCTGTTTCTTTTTGGACTGCTTTAATTTGTGGGAAGATATTTTCTGTCACAAATTCATCAT CTGTCATCGCTTCAAGTTTTGCTTTGAATGCTTCAAGAACTGTTGGAACTGTTTCACCCGTCATGACTTC GCGCTCTGCTTCTGTCAATTCTGGGAAATCTGAGAAGAAAAGATCTGTCAATGGGATAATCTCATCTACT GATTTCATTTGTGGTTTATAGAGCTCAACTAATTTTTCAGCCTTGTCAGTCAAACGGCCTGCTTCCTCTA AGAATGGTTTTGCCATTTCAAAGATGGTTTCAAGGTCTGCATTCTTGATATAATCATTGCTCATCCAGTC TAGTTTTTTCTGATCAAAGGCTGCTGGTGACTTGCTGAGGCGGTTTTCATCAAAAAGTTTAATGAATTCT TCACGAGAGAAAATCTCATCTTCACCACCTGGGTTCCAACCAAGAAGAGCAATAAAGTTAAAGACTGCTT CTGGAAGGTAACCTTTCTTTCGGTAATCTTCGATAAATTGAAGTGTATTAGTATCACGTTTAGATAACTT CTTACCAGTTTCAGAGTTGATAATCAAGGTCATGTGACCGAACTCTGGAGCTTCCCAACCAAGAGCTTCA TAGACCATAAGCTGTTTTGGTGTATTAGCAATATGGTCATCTCCACGGATAACATGAGAGATTTGCATAT CGTGGTCATCGATAACAACGGCAAAGTTGTAAGTTGGGTAACCGTCTTTCTTTTGGATAACCCAGTCACC ACCGATATTGCCACCTTCAAATTCGATATCGCCTTTGACCATATCATGCCACTTGTAGATACCTGACTCA TTGACAGCCAAACGAACAGTTGGGATGATCCCTGCTGCTTCACGTTCTGCGATGTAAGCTGCTTTTTCTT CTTCACTCATACCAAGGTATTCATTGATGTAGCGTGGTGTTTCGCCAGCTACTTCTTGGCGTTCGCGTTC AGCTGCCAACTCTTCTTCTGTAACGTAAGATTTATAGGCTTTTCCTTCAGCTAATAGTTGGTCAATATAT TTTTGATACAAGTCCAAACGCTCAGACTGGCGATAATTCTCATGTGATTCTGGACTTTCATCCCAATCCA TGCCTAACCAGCGAAGGTTTTCAAGTTGTGAACGTTCACCATCCTCGACATGGCGTTTACGGTCAGTATC TTCGATACGGATGAGAAATGTTCCACCATGATGGCGCGCATACAAGTAATTAAACAATGCTGTACGAGCA TTTCCGATGTGTAGTAGTCCTGTTGGACTTGGTGCGTAACGTACGCGGATATCTTTTGACA >WP_000031087.1 glutamate--tRNA ligase [Streptococcus pneumoniae] MSKDIRVRYAPSPTGLLHIGNARTALFNYLYARHHGGTFLIRIEDTDRKRHVEDGERSQLENLRWLGMDW DESPESHENYRQSERLDLYQKYIDQLLAEGKAYKSYVTEEELAAERERQEVAGETPRYINEYLGMSEEEK AAYIAEREAAGIIPTVRLAVNESGIYKWHDMVKGDIEFEGGNIGGDWVIQKKDGYPTYNFAVVIDDHDMQ ISHVIRGDDHIANTPKQLMVYEALGWEAPEFGHMTLIINSETGKKLSKRDTNTLQFIEDYRKKGYLPEAV FNFIALLGWNPGGEDEIFSREEFIKLFDENRLSKSPAAFDQKKLDWMSNDYIKNADLETIFEMAKPFLEE AGRLTDKAEKLVELYKPQMKSVDEIIPLTDLFFSDFPELTEAEREVMTGETVPTVLEAFKAKLEAMTDDE FVTENIFPQIKAVQKETGIKGKNLFMPIRIAVSGEMHGPELPDTIFLLGREKSIQHIENMLKEISK Protective antigen Glutamyl tRNA synthetase (GtS) has been found to be among the Streptococcus pneumoniae cell wall-derived proteins that have age-dependent immunogenicity in children. Here, GtS was cloned, expressed, and purified and then was used to immunize 7-week-old BALB/c OlaHsd mice. Thirty-nine percent of rGtS-immunized mice survived a lethal bacterial challenge, whereas no control mice survived [Ref1210:Mizrachi et al., 2007]. Gnd Streptococcus pneumoniae D39 VO_0011206 4441177 WP_000158781 SPD_0343 CP000410 YP_815856 CDD:236453 1301 347261 348685 + NADP-dependent phosphogluconate dehydrogenase 4.58 51871.44 574 6-phosphogluconate dehydrogenase; Validated >NC_008533.1:347261-348685 Streptococcus pneumoniae D39, complete genome AATGACAAAAGCTAACTTTGGTGTCGTAGGTATGGCCGTAATGGGTCGTAACCTTGCCCTTAATATTGAA TCACGTGGTTACACAGTTGCTATCTACAACCGTAGTAAAGAAAAAACGGAAGATGTGATTGCTTGCCATC CTGAAAAGAATTTTGTACCAAGCTATGACGTTGAAAGTTTTGTAAACTCAATCGAAAAACCTCGTCGTAT CATGCTGATGGTTCAAGCTGGACCTGGTACAGATGCTACTATTCAAGCCCTTCTTCCGCACCTTGACAAG GGTGATATCTTGATTGACGGTGGAAATACTTTCTACAAAGATACCATCCGTCGTAATGAAGAATTGGCAA ACTCTGGTATCAACTTTATCGGTACTGGGGTTTCTGGTGGTGAAAAAGGTGCCCTTGAAGGTCCTTCTAT CATGCCTGGTGGACAAAAAGAAGCCTACGAATTGGTTGCGGATGTTCTTGAAGAAATCTCAGCTAAAGCA CCAGAAGATGGCAAACCATGTGTGACTTACATCGGTCCTGATGGAGCTGGTCACTATGTGAAAATGGTTC ACAATGGTATTGAGTACGGTGATATGCAATTGATCGCAGAAAGCTATGACTTGATGCAACACTTGCTAGG CCTTTCTGCAGAAGATATGGCTGAAATCTTTACTGAGTGGAACAAGGGTGAATTAGACAGCTACTTGATT GAAATCACAGCTGATATCTTGAGCCGTAAAGACGATGAAGGCCAAGATGGACCAATCGTAGACTACATCC TTGATGCTGCAGGTAACAAGGGAACTGGTAAATGGACTAGCCAATCATCTCTTGACCTTGGTGTACCATT GTCACTGATTACTGAGTCAGTGTTTGCACGCTACATTTCAACTTACAAAGAAGAACGTGTACATGCTAGC AAGGTGCTTCCAAAACCAGCTGCCTTCAACTTTGAAGGAGACAAGGCTGAATTGATTGAAAAGATCCGTC AAGCCCTTTACTTCTCAAAAATCATTTCATACGCACAAGGATTTGCTCAATTGCGTGTAGCCTCTAAAGA AAACAACTGGAACTTGCCATTTGCAGATATCGCATCTATCTGGCGTGATGGCTGTATCATCCGTTCTCGT TTCTTGCAAAAGATTACAGATGCTTACAACCGCGATGCAGATCTTGCCAACCTTCTTTTGGACGAGTACT TCTTGGATGTTACTGCTAAGTACCAACAAGCAGTACGTGATATCGTAGCTCTTGCGGTTCAAGCAGGTGT GCCAGTGCCAACTTTCTCAGCAGCTATTACTTACTTTGATAGCTACCGTTCAGCTGACCTTCCAGCTAAC TTGATCCAAGCACAACGTGACTACTTTGGTGCTCACACTTACCAACGTAAAGACAAAGAAGGAACCTTCC ACTACTCTTGGTATGACGAAAAATA >WP_000158781.1 MULTISPECIES: NADP-dependent phosphogluconate dehydrogenase [Streptococcus] MTKANFGVVGMAVMGRNLALNIESRGYTVAIYNRSKEKTEDVIACHPEKNFVPSYDVESFVNSIEKPRRI MLMVQAGPGTDATIQALLPHLDKGDILIDGGNTFYKDTIRRNEELANSGINFIGTGVSGGEKGALEGPSI MPGGQKEAYELVADVLEEISAKAPEDGKPCVTYIGPDGAGHYVKMVHNGIEYGDMQLIAESYDLMQHLLG LSAEDMAEIFTEWNKGELDSYLIEITADILSRKDDEGQDGPIVDYILDAAGNKGTGKWTSQSSLDLGVPL SLITESVFARYISTYKEERVHASKVLPKPAAFNFEGDKAELIEKIRQALYFSKIISYAQGFAQLRVASKE NNWNLPFADIASIWRDGCIIRSRFLQKITDAYNRDADLANLLLDEYFLDVTAKYQQAVRDIVALAVQAGV PVPTFSAAITYFDSYRSADLPANLIQAQRDYFGAHTYQRKDKEGTFHYSWYDEK Protective antigen BALB/c mice were immunized with recombinant 6-Phosphogluconate dehydrogenase (r6PGD) and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge [Ref1213:Daniely et al., 2006]. phpA Streptococcus pneumoniae VO_0012383 NP_358654 CDD:273578 CDD:282170 CDD:293251 171101 ? histidine motif-containing protein 5.38 92561.31 947 streptococcal histidine triad protein; TIGR01363 >NP_358654.1 histidine motif-containing protein [Streptococcus pneumoniae R6] MNQIYLRKEERMKINKKYLAGSVATLVLSVCAYELGLHQAQTVKENNRVSYIDGKQATQKTENLTPDEVS KREGINAEQIVIKITDQGYVTSHGDHYHYYNGKVPYDAIISEELLMKDPNYQLKDEDIISEIKGGYVIKV DGKYYVYLKDAAHADNVRTKEEINRQKQEHSQHREGGTPRNDGAVALARSQGRYTTDDGYIFNASDIIED TGDAYIVPHGDHYHYIPKNELSASELAAAKAFLSGRGNLSNSRTYRRQNSDNTSRTNWVPSVSNPGTTNT NTSNNSNTNSQASQSNDIDSLLKQLYKLPLSQRHVESDGLIFDPAQITSRTANGVAVPHGDHYHFIPYSQ LSPLEEKLARIIPLRYRSNHWVPDSRPEQPSPQSTPEPSPSPQPAPNPQPAPSNPIDEKLVKEAVRKVGD GYVFEENGVPRYIPAKDLSAETAAGIDSKLAKQESLSHKLGAKKTDLPSSDREFYNKAYDLLARIHQDLL DNKGRQVDFEALDNLLERLKDVSSDKVKLVDDILAFLAPIRHPERLGKPNAQITYTDDEIQVAKLAGKYT TEDGYIFDPRDITSDEGDAYVTPHMTHSHWIKKDSLSEAERAAAQAYAKEKGLTPPSTDHQDSGNTEAKG AEAIYNRVKAAKKVPLDRMPYNLQYTVEVKNGSLIIPHYDHYHNIKFEWFDEGLYEAPKGYSLEDLLATV KYYVEHPNERPHSDNGFGNASDHVQRNKNGQADTNQTEKPNEEKPQTEKPEEETPREEKPQSEKPESPKP TEEPEEESPEESPEESEEPQVETEKVKEKLREAEDLLGKIQNPIIKSNAKETLTGLKNNLLFGTQDNNTI MAEAEKLLALLKESK Protective antigen Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain [Ref1492:Zhang et al., 2001]. PiaA Streptococcus pneumoniae D39 VO_0011207 4442863 WP_000731179 SPD_0226 CP000410 YP_815744 CDD:328725 1313 216000 216368 - extracellular solute-binding protein 4.84 35132.62 424 Type 2 periplasmic binding fold superfamily; cl21456 >NC_008533.1:216000-216368 Streptococcus pneumoniae D39, complete genome TTTACTGTTTAGATTGGATATCTGTAAAGACTTCGTTGTATTTCTTAACGATATCTGATTTATTCTTGAT GACATAATCATAATCTTCAGTGAGTGTTTTGATTTTGTCAATTGGTTTCATGTTTTCGCTTGTTTTAGCA TTTTTACGAACAGGACGGTTAGTAGTGGTTGTACCAAGTGTATCTTGTACTTCTTGAGAGATAATAAAAT CGATAAATTTCTTGGCATTTTCCATATTTTTAGATTTTTTAACGATAGCAGCACTAGCAGGTAGGAAGAC GGTTCCTTCTTTTGGATAGACTACTTTAATGTTAGCTCCGTCATTTAAGAGTTTAACTGCTGAATCTTCA TAAGAGAGACCAACAGTCA >WP_000731179.1 extracellular solute-binding protein [Streptococcus pneumoniae] MKKKWMYYAACSSNESADDSSSDKGDGGSLVVYSPNSEGLIGATIPAFEEKYGIKVELIQAGTGELFKKL ESEKEVPVADVIFGGSYTQYTTHGELFENYTSKENDNVIKEYQNTTGYSTPYTLDGSVLIVNPDLTKGMN IEGYNDLFKPELKGKIATADPANSSSAFAQLTNMLQAQGGYKDDKAWSYVKDLFTLIDGKIGSSSSSVYK VVADGEMAVGLSYEDPAVKLLNDGANIKVVYPKEGTVFLPASAAIVKKSKNMENAKKFIDFIISQEVQDT LGTTTTNRPVRKNAKTSENMKPIDKIKTLTEDYDYVIKNKSDIVKKYNEVFTDIQSKQ Protective antigen Mice immunized with recombinant PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae [Ref1214:Brown et al., 2001]. PlyD1 ? >detoxified pneumolysin [Streptococcus pneumoniae] MANKAVNDFILAMNYDKKKLLTHQGESIENRFIKEGNQLPDEFVVIERKKRSLSTNTSDISVTACNDSRL YPGALLVVDETLLENNPTLLAVDRAPMTYSIDLPGLASSDSFLQVEDPSNSSVRGAVNDLLAKWHQDYGQ VNNVPARMQYEKITAHSMEQLKVKFGSDFEKTGNSLDIDFNSVHSGEKQIQIVNFKQIYYTVSVDAVKNP GDVFQDTVTVEDLKQRGISAERPLVYISSVAYGRQVYLKLETTSKSDEVEAAFEALIKGVKVAPQTEWKQ ILDNTEVKAVILGCDPSSGARVVTGKVDMVEDLIQEGSRFTADHPGLPISYTTSFLRDNVVATFQNSTDY VETKVTAYRNGDLLLDHSGAYVAQYYITWNELSYDHQGKEVLTPKAWDRNGQDLTAHFTTSIPLKGNVRN LSVKIREATGLAWEWWRTVYEKTDLPLVRKRTISIWGTTLYPQVEDKVEND Protective antigen Results have shown that PlyD1 immunization protected mice against lethal intranasal (i.n.) challenge with pneumococci and lung injury mediated by PLY challenge. [Ref5093:Salha et al., 2012] PlyD1 significantly reduced bacterial burden in MEF at 48 hpi (p = 0.02)[Ref4728:Xu et al., 2017] psaA Streptococcus pneumoniae VO_0011190 NP_359087 1PSZ CDD:238557 171101 ? ABC transporter substrate-binding protein - manganese transport 5.19 33579.58 421 Metal binding protein PsaA. These proteins have been shown to function as initial receptors in ABC transport of Mn2+ and as surface adhesins in some eubacterial species. They belong to the TroA superfamily of periplasmic metal binding proteins that...; cd01137 >AAL00298.1 ABC transporter substrate-binding protein - manganese transport [Streptococcus pneumoniae R6] MKKLGTLLVLFLSAIILVACASGKKDTTSGQKLKVVATNSIIADITKNIAGDKIDLHSIVPIGQDPHEYE PLPEDVKKTSEADLIFYNGINLETGGNAWFTKLVENAKKTENKDYFAVSDGVDVIYLEGQNEKGKEDPHA WLNLENGIIFAKNIAKQLSAKDPNNKEFYEKNLKEYTDKLDKLDKESKDKFNKIPAEKKLIVTSEGAFKY FSKAYGVPSAYIWEINTEEEGTPEQIKTLVEKLRQTKVPSLFVESSVDDRPMKTVSQDTNIPIYAQIFTD SIAEQGKEGDSYYSMMKYNLDKIAEGLAK Protective antigen Vaccination with an RASV synthesizing full-length PsaA induced high titers of anti-PsaA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes, nasal washes, and lung homogenates) sites. BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains. None of the vaccine constructs provided protection against intraperitoneal challenge with S. pneumoniae strain WU2 (serotype 3) [Ref1202:Wang et al., 2010]. The results of colonization experiment showed that compared with the control group, the PepO, PsaA, and combined immunization groups showed a significant reduction in the colonization of Streptococcus pneumoniae (CMCC31693 and CMCC31207) in the nasopharynx and lung (P<0.05).[Ref4933:Zhang et al., 2017] PspA Streptococcus pneumoniae D39 VO_0011204 4441373 116515876 SPD_0126 CP000410 YP_815641 373153 128355 130214 + surface protein A 4.82 66023.6 619 equivalent gene in S.pneumoniae R6 = spr0121; identified by match to protein family HMM PF01473 >NC_008533.1:128355-130214 Streptococcus pneumoniae D39, complete genome GATGAATAAGAAAAAAATGATTTTAACAAGTCTAGCCAGCGTCGCTATCTTAGGGGCTGGTTTTGTTGCG TCTCAGCCTACTGTTGTAAGAGCAGAAGAATCTCCCGTAGCCAGTCAGTCTAAAGCTGAGAAAGACTATG ATGCAGCGAAGAAAGATGCTAAGAATGCGAAAAAAGCAGTAGAAGATGCTCAAAAGGCTTTAGATGATGC AAAAGCTGCTCAGAAAAAATATGACGAGGATCAGAAGAAAACTGAGGAGAAAGCCGCGCTAGAAAAAGCA GCGTCTGAAGAGATGGATAAGGCAGTGGCAGCAGTTCAACAAGCGTATCTAGCCTATCAACAAGCTACAG ACAAAGCCGCAAAAGACGCAGCAGATAAGATGATAGATGAAGCTAAGAAACGCGAAGAAGAGGCAAAAAC TAAATTTAATACTGTTCGAGCAATGGTAGTTCCTGAGCCAGAGCAGTTGGCTGAGACTAAGAAAAAATCA GAAGAAGCTAAACAAAAAGCACCAGAACTTACTAAAAAACTAGAAGAAGCTAAAGCAAAATTAGAAGAGG CTGAGAAAAAAGCTACTGAAGCCAAACAAAAAGTGGATGCTGAAGAAGTCGCTCCTCAAGCTAAAATCGC TGAATTGGAAAATCAAGTTCATAGACTAGAACAAGAGCTCAAAGAGATTGATGAGTCTGAATCAGAAGAT TATGCTAAAGAAGGTTTCCGTGCTCCTCTTCAATCTAAATTGGATGCCAAAAAAGCTAAACTATCAAAAC TTGAAGAGTTAAGTGATAAGATTGATGAGTTAGACGCTGAAATTGCAAAACTTGAAGATCAACTTAAAGC TGCTGAAGAAAACAATAATGTAGAAGACTACTTTAAAGAAGGTTTAGAGAAAACTATTGCTGCTAAAAAA GCTGAATTAGAAAAAACTGAAGCTGACCTTAAGAAAGCAGTTAATGAGCCAGAAAAACCAGCTCCAGCTC CAGAAACTCCAGCCCCAGAAGCACCAGCTGAACAACCAAAACCAGCGCCGGCTCCTCAACCAGCTCCCGC ACCAAAACCAGAGAAGCCAGCTGAACAACCAAAACCAGAAAAAACAGATGATCAACAAGCTGAAGAAGAC TATGCTCGTAGATCAGAAGAAGAATATAATCGCTTGACTCAACAGCAACCGCCAAAAGCTGAAAAACCAG CTCCTGCACCAAAAACAGGCTGGAAACAAGAAAACGGTATGTGGTACTTCTACAATACTGATGGTTCAAT GGCGACAGGATGGCTCCAAAACAACGGTTCATGGTACTACCTCAACAGCAATGGTGCTATGGCTACAGGT TGGCTCCAATACAATGGTTCATGGTATTACCTCAACGCTAACGGCGCTATGGCAACAGGTTGGGCTAAAG TCAACGGTTCATGGTACTACCTCAACGCTAATGGTGCTATGGCTACAGGTTGGCTCCAATACAACGGTTC ATGGTATTACCTCAACGCTAACGGCGCTATGGCAACAGGTTGGGCTAAAGTCAACGGTTCATGGTACTAC CTCAACGCTAATGGTGCTATGGCTACAGGTTGGCTCCAATACAACGGTTCATGGTACTACCTCAACGCTA ACGGTGCTATGGCTACAGGTTGGGCTAAAGTCAACGGTTCATGGTACTACCTCAACGCTAATGGTGCTAT GGCAACAGGTTGGGTGAAAGATGGAGATACCTGGTACTATCTTGAAGCATCAGGTGCTATGAAAGCAAGC CAATGGTTCAAAGTATCAGATAAATGGTACTATGTCAATGGTTTAGGTGCCCTTGCAGTCAACACAACTG TAGATGGCTATAAAGTCAATGCCAATGGTGAATGGGTTTA >YP_815641.1 surface protein A [Streptococcus pneumoniae D39] MNKKKMILTSLASVAILGAGFVASQPTVVRAEESPVASQSKAEKDYDAAKKDAKNAKKAVEDAQKALDDA KAAQKKYDEDQKKTEEKAALEKAASEEMDKAVAAVQQAYLAYQQATDKAAKDAADKMIDEAKKREEEAKT KFNTVRAMVVPEPEQLAETKKKSEEAKQKAPELTKKLEEAKAKLEEAEKKATEAKQKVDAEEVAPQAKIA ELENQVHRLEQELKEIDESESEDYAKEGFRAPLQSKLDAKKAKLSKLEELSDKIDELDAEIAKLEDQLKA AEENNNVEDYFKEGLEKTIAAKKAELEKTEADLKKAVNEPEKPAPAPETPAPEAPAEQPKPAPAPQPAPA PKPEKPAEQPKPEKTDDQQAEEDYARRSEEEYNRLTQQQPPKAEKPAPAPKTGWKQENGMWYFYNTDGSM ATGWLQNNGSWYYLNSNGAMATGWLQYNGSWYYLNANGAMATGWAKVNGSWYYLNANGAMATGWLQYNGS WYYLNANGAMATGWAKVNGSWYYLNANGAMATGWLQYNGSWYYLNANGAMATGWAKVNGSWYYLNANGAM ATGWVKDGDTWYYLEASGAMKASQWFKVSDKWYYVNGLGALAVNTTVDGYKVNANGEWV Protective antigen Groups of BALB/c mice immunized with choline binding protein PspA were challenged with either D39 or WCH16. PspA elicited protection by using moderate challenge doses of S. pneumoniae [Ref1212:Ogunniyi et al., 2007]. SrtA Streptococcus pneumoniae D39 VO_0011199 4442999 116515518 SPD_1076 CP000410 YP_816547 373153 1102250 1102993 - sortase 5.46 26445.89 247 equivalent gene in S.pneumoniae TIGR4 = SP1218; equivalent gene in S.pneumoniae R6 = spr1098; identified by match to protein family HMM PF04203; match to protein family HMM TIGR01076 >NC_008533.1:1102250-1102993 Streptococcus pneumoniae D39, complete genome ATTAATAAAATTGTTTATATGGTTGATTGAAAGCTGTTAGGATTTCATCAGATGTTTGTGAATAATCTTT TGTTTCTTTCAAATCACCTTTGACAATAATACGTTCTGTAGCAGCAAGGTCTTCACAGGTTACTAATGTG ATTTCATTGACCCCATCTCTATCATCAACTTCATCAACACGATCTGGTGTCACACGTTTGACTTCACGTA TTTCATAAGTATAAACTTTATTTTTATCGGTTAGATAAATCTTCATGCCATTTTTAGCATTATCTAAAGG AGAAAATAACATTTTATTAGCATTATCAACACCAAAGATATGGTGACTAGCTAGACTATAATTTCCTTCT CCCATTACTTGCTCGCGTTTCATTGTACCAGCTCCGTAGAAGAGATTAACATTATCAAGTCCTTTAAAAA TCGGCAAATTCATTTCCAATTCAGGAATTGCAATTCCCCCAATAACTGGTAATTTTTGAGCATCCCATTG AGAAGTTAGAACAGCTTCCGAAGAGATAGCTTTGACAGAATCAAAGTCAAAATTGCCTTCTGTATCCTGA TTTTCTTCTAATTTTTCTTTTGATACCTGGCTAACTTGATACTTATTGGTATTCCAGACTATGAAAATAT TTCGAATTTGAGTATTAAAAATCAAAGCCAGTGACAGTAATATCAGAAATCCTGCTAGGATATTTGTCAG CAGATTTTTTCGCTTGTTTTTCTTTTTATTATTTTTTTGAGACA >YP_816547.1 sortase [Streptococcus pneumoniae D39] MSQKNNKKKNKRKNLLTNILAGFLILLSLALIFNTQIRNIFIVWNTNKYQVSQVSKEKLEENQDTEGNFD FDSVKAISSEAVLTSQWDAQKLPVIGGIAIPELEMNLPIFKGLDNVNLFYGAGTMKREQVMGEGNYSLAS HHIFGVDNANKMLFSPLDNAKNGMKIYLTDKNKVYTYEIREVKRVTPDRVDEVDDRDGVNEITLVTCEDL AATERIIVKGDLKETKDYSQTSDEILTAFNQPYKQFY Protective antigen Intraperitoneal immunization with recombinant SrtA was found to have conferred to mice protection against S. pneumoniae intraperitoneal challenge and the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA was observed, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen [Ref1208:Gianfaldoni et al., 2009]. 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