Current status and perspectives on protein-based pneumococcal vaccines

Critical Reviews in Microbiology

Volumn 41, Issue 2, 2015, Pages 190-200

  Darrieux, Michelle ^a   Goulart, Cibelly ^b,c   Briles, David ^d   Leite, Luciana Cezar De Cerqueira ^b  

^a UNIVERSIDADE SÃO FRANCISCO   (Brazil)

^b INSTITUTO BUTANTAN   (Brazil)

^c UNIVERSITY OF SÃO PAULO   (Brazil)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Pneumococcal proteins; Streptococcus pneumoniae; Vaccine

Indexed keywords

BACTERIAL PROTEIN; PNEUMOCOCCAL CHOLINE BINDING PROTEIN A; PNEUMOCOCCAL PROTECTIVE PROTEIN A; PNEUMOCOCCAL SURFACE ANTIGEN A; PNEUMOCOCCAL SURFACE PROTEIN A; PNEUMOCOCCUS VACCINE; PNEUMOLYSIN; PROTEIN PCSB; PROTEIN PHT; PROTEIN POTD; PROTEIN SERINE THREONINE KINASE; SIALIDASE; UNCLASSIFIED DRUG; WHOLE CELL PNEUMOCOCCAL VACCINE; BACTERIAL ANTIGEN; RECOMBINANT VACCINE;

BACTERIUM PILUS; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOGENICITY; NONHUMAN; OTITIS MEDIA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMOCOCCAL INFECTION; PNEUMONIA; PRIORITY JOURNAL; REVIEW; STREPTOCOCCUS PNEUMONIAE; DRUG DEVELOPMENT; GENETICS; IMMUNOLOGY; ISOLATION AND PURIFICATION; PNEUMOCOCCAL INFECTIONS; TRENDS;

BACTERIA (MICROORGANISMS); STREPTOCOCCUS PNEUMONIAE;

ANTIGENS, BACTERIAL; BACTERIAL PROTEINS; DRUG DISCOVERY; HUMANS; PNEUMOCOCCAL INFECTIONS; PNEUMOCOCCAL VACCINES; STREPTOCOCCUS PNEUMONIAE; VACCINES, SYNTHETIC;

EID: 84929742545     PISSN: 1040841X     EISSN: 15497828     Source Type: Journal    
DOI: 10.3109/1040841X.2013.813902     Document Type: Review

References (157)

1. Adamou JE, Heinrichs JH, Erwin AL, et al. (2001). IDentification and characterization of a novel family of pneumococcal proteins that are protective against sepsis. Infection and immunity 69:949-58
2. Agnandji ST, Lell B, Soulanoudjingar SS, et al. (2011). First results of phase 3 trial of Rts, S/AS01 malaria vaccine in African children. N Engl J Med 365:1863-75
3. Agnandji ST, Lell B, FernanDes JF, et al. (2012). A phase 3 trial of RTS, S/AS01 malaria vaccine in African infants. N Engl J Med 367: 2284-95
4. Alcantara RB, Preheim LC, GENTRY-Nielsen MJ. (2001). Pneumolysininduced complement Depletion during experimental pneumococcal bacteremia. Infect Immun 69:3569-75
5. Arulanandam BP, Lynch JM, Briles DE, et al. (2001). Intranasal vaccination with pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection. Infect Immun 69: 6718-24
6. Audouy SA, Van Selm S, Van Roosmalen ML, et al. (2007). Development of lactococcal GEM-based pneumococcal vaccines. Vaccine 25: 2497-506
7. Balachandran P, Brooks-Walter A, Virolainen-Julkunen A, et al. (2002). Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae. Infect Immun 70:2526-34
8. Baril L, Briles DE, Crozier P, et al. (2004). Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease. Vaccine 23:789-93
9. Barocchi MA, Ries J, Zogaj X, et al. (2006). A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A 103:2857-62
10. Beghetto E, Gargano N, Ricci S, et al. (2006). Discovery of novel Streptococcus pneumoniae antigens by screening a whole-genome lambda-display library. FEMS Microbiol Lett 262:14-21
11. Berry AM, AlexanDer JE, Mitchell TJ, et al. (1995). Effect of Defined point mutations in the pneumolysin gene on the virulence of Streptococcus pneumoniae. Infect Immun 63:1969-74
12. Berry AM, Paton JC. (1996). Sequence heterogeneity of Psaa, a 37-kilodalton putative adhesin essential for virulence of Streptococcus pneumoniae. Infect Immun 64:5255-62
13. Bologa M, Kamtchoua T, Hopfer R, et al. (2012). Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpApneumococcal histidine triad protein D vaccine. Vaccine 30:7461-8
14. Briles DE, ADes E, Paton JC, et al. (2000a). Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae. Infect Immun 68:796-800
15. Briles DE, Hollingshead SK, King J, et al. (2000b). Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA. J Infect Dis 182:1694-701
16. Briles DE, Hollingshead SK, Nabors GS, et al. (2000c) the potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae. Vaccine 19:S87-95
17. Briles DE, Hollingshead SK, Paton JC, et al. (2003). Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine moDel of pulmonary infection with Streptococcus pneumoniae. J Infect Dis 188:339-48
18. Brooks-Walter A, Briles DE, Hollingshead SK. (1999) the pspC gene of Streptococcus pneumoniae encoDes a polymorphic protein, Pspc, which elicits cross-reactive antibodies to PspA and proviDes immunity to pneumococcal bacteremia. Infect Immun 67:6533-42
19. Brown JS, Gilliland SM, HolDen DW. (2001a). A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence. Mol Microbiol 40:572-85
20. Brown JS, Ogunniyi AD, Woodrow MC, et al. (2001b). Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection. Infect Immun 69:6702-6
21. Campos IB, Darrieux M, Ferreira DM, et al. (2008). Nasal immunization of mice with Lactobacillus casei expressing the Pneumococcal Surface Protein A: induction of antibodies, complement Deposition and partial protection against Streptococcus pneumoniae challenge. Microbes Infect 10:481-8
22. Cao J, Chen D, Xu W, et al. (2007). Enhanced protection against pneumococcal infection elicited by immunization with the combination of Pspa, Pspc, and ClpP. Vaccine 25:4996-5005
23. Cao J, Chen T, Li D, et al. (2008). Mucosal immunization with purified ClpP could elicit protective efficacy against pneumococcal pneumonia and sepsis in mice. Microbes Infect 10:1536-42
24. Cardaci A, Papasergi S, Midiri A, et al. (2012). Protective activity of Streptococcus pneumoniae Spr1875 protein fragments iDentified using a phage displayed genomic library. PLoS One 7: e36588
25. Csordas FC, Perciani CT, Darrieux M, et al. (2008). Protection induced by pneumococcal surface protein A (PspA) is enhanced by conjugation to a Streptococcus pneumoniae capsular polysacchariDe. Vaccine 26:2925-9
26. Cui Y, Zhang X, Gong Y, et al. (2011). Immunization with DnaJ (hsp40) could elicit protection against nasopharyngeal colonization and invasive infection caused by different strains of Streptococcus pneumoniae. Vaccine 29:1736-44
27. Daniels CC, Coan P, King J, et al. (2010) the proline-rich region of pneumococcal surface proteins A and C contains surface-Accessible epitopes common to all pneumococci and elicits antibody-mediated protection against sepsis. Infect Immun 78:2163-72
28. Darrieux M, Miyaji EN, Ferreira DM, et al. (2007). Fusion proteins containing family 1 and family 2 PspA fragments elicit protection against Streptococcus pneumoniae that correlates with antibodymediated enhancement of complement Deposition. Infect Immun 75: 5930-8
29. Darrieux M, Moreno AT, Ferreira DM, et al. (2008). Recognition of pneumococcal isolates by antisera raised against PspA fragments from different claDes. J Med Microbiol 57:273-8
30. Dave S, Brooks-Walter A, Pangburn MK, Mcdaniel LS. (2001). Pspc, a pneumococcal surface protein, binds human factor H. Infect Immun 69:3435-7
31. Dave S, Carmicle S, Hammerschmidt S, et al. (2004a). Dual roles of Pspc, a surface protein of Streptococcus pneumoniae, in binding human secretory IgA and factor H. J Immunol 173:471-7
32. Dave S, Pangburn MK, Pruitt C, Mcdaniel LS. (2004b). Interaction of human factor H with PspC of Streptococcus pneumoniae. Indian J Med Res 119:66-73
33. De Angelis G, Moschioni M, Muzzi A, et al. (2011) the Streptococcus pneumoniae pilus-1 displays a biphasic expression pattern. PLoS One 6:e21269
34. Denoel P, Godfroid F, Hermand P, et al. (2011a). Combined protective effects of anti-PhTD and anti-pneumococcal polysacchariDes. Vaccine 29:6451-3
35. Denoel P, Philipp MT, Doyle L, et al. (2011b). A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae. Vaccine 29:5495-501
36. Dintilhac A, Alloing G, GranaDel C, Claverys JP. (1997). Competence and virulence of Streptococcus pneumoniae: Adc and PsaA mutants exhibit a requirement for Zn and Mn resulting from inactivation of putative ABC metal permeases. Mol Microbiol 25:727-39
37. Ferreira DM, Areas AP, Darrieux M, et al. (2006). DNA vaccines based on genetically Detoxified Derivatives of pneumolysin fail to protect mice against challenge with Streptococcus pneumoniae. FEMS Immunol Med Microbiol 46:291-7
38. Ferreira DM, Darrieux M, Silva DA, et al. (2009). Characterization of protective mucosal and systemic immune responses elicited by pneumococcal surface protein PspA and PspC nasal vaccines against a respiratory pneumococcal challenge in mice. Clin Vaccine Immunol 16:636-45
39. Ferreira DM, Oliveira ML, Moreno AT, et al. (2010). Protection against nasal colonization with Streptococcus pneumoniae by parenteral immunization with a DNA vaccine encoding PspA (Pneumococcal surface protein A). Microb Pathog 48:205-13
40. Gianfaldoni C, Censini S, Hilleringmann M, et al. (2007). Streptococcus pneumoniae pilus subunits protect mice against lethal challenge. Infect Immun 75:1059-62
41. Gianfaldoni C, Maccari S, Pancotto L, et al. (2009). Sortase A confers protection against Streptococcus pneumoniae in mice. Infec Immun 77:2957-61
42. Giefing C, Jelencsics KE, Gelbmann D, et al. (2010) the pneumococcal eukaryotic-type serine/threonine protein kinase StkP co-localizes with the cell division apparatus and interacts with FtsZ in vitro. Microbiology 156:1697-707
43. Giefing C, Meinke AL, Hanner M, et al. (2008). Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J Exp Med 205:117-31
44. Glover DT, Hollingshead SK, Briles DE. (2008). Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infec Immun 76:2767-76
45. Godfroid F, Hermand P, Verlant V, et al. (2011). Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infec Immun 79:238-45
46. Gong Y, Xu W, Cui Y, et al. (2011). Immunization with a ZmpB-based protein vaccine could protect against pneumococcal diseases in mice. Infect Immun 79:867-78
47. Gor DO, Ding X, Briles DE, et al. (2005). Relationship between surface accessibility for Ppma, Psaa, and PspA and antibody-mediated immunity to systemic infection by Streptococcus pneumoniae. Infect Immun 73:1304-12
48. Goulart C, DA Silva TR, Rodriguez D, et al. (2013). Characterization of protective immune responses induced by pneumococcal surface protein A in fusion with pneumolysin Derivatives. PLoS One 8:e59605
49. Goulart C, Darrieux M, Rodriguez D, et al. (2011). Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement Deposition and opsonophagocytosis by murine peritoneal cells. Vaccine 29:1634-42
50. Green BA, Zhang Y, Masi AW, et al. (2005). Pppa, a surface-exposed protein of Streptococcus pneumoniae, elicits cross-reactive antibodies that reduce colonization in a murine intranasal immunization and challenge moDel. Infect Immun 73:981-9
51. Hamel J, Charland N, Pineau I, et al. (2004). Prevention of pneumococcal disease in mice immunized with conserved surface-Accessible proteins. Infect Immun 72:2659-70
52. Harfouche C, Filippini S, Gianfaldoni C, et al. (2012). RrgB321, a fusion protein of the three variants of the pneumococcal pilus backbone Rrgb, is protective in vivo and elicits opsonic antibodies. Infect Immun 80:451-60
53. Hava DL, Camilli A. (2002). Large-scale iDentification of serotype 4 Streptococcus pneumoniae virulence factors. Molecular microbiology 45:1389-406
54. Hernani M De L, Ferreira PC, Ferreira DM, et al. (2011). Nasal immunization of mice with Lactobacillus casei expressing the pneumococcal surface protein C primes the immune system and Decreases pneumococcal nasopharyngeal colonization in mice. FEMS Immunol Med Microbiol 62:263-72
55. Hilleringmann M, Ringler P, Muller SA, et al. (2009). Molecular architecture of Streptococcus pneumoniae TIGR4 pili. EMBO J 28: 3921-30
56. Hollingshead SK, Becker R, Briles DE. (2000). Diversity of PspA: mosaic genes and eviDence for past recombination in Streptococcus pneumoniae. Infect Immun 68:5889-900
57. Holmlund E, Quiambao B, Ollgren J, et al. (2009). Antibodies to pneumococcal proteins Phtd, Cbpa, and LytC in Filipino pregnant women and their infants in relation to pneumococcal carriage. Clin Vaccine Immunol 16:916-23
58. Hoskins J, Alborn JR WE, Arnold J, et al. (2001). Genome of the bacterium Streptococcus pneumoniae strain R6. J Bacteriol 183: 5709-17
59. Iannelli F, Oggioni MR, Pozzi G. (2002). Allelic variation in the highly polymorphic locus pspC of Streptococcus pneumoniae. Gene 284: 63-71
60. Johnston JW, Briles DE, Myers LE, Hollingshead SK. (2006). Mn2DepenDent regulation of multiple genes in Streptococcus pneumoniae through PsaR and the resultant impact on virulence. Infec Immun 74: 1171-80
61. Jomaa M, Terry S, Hale C, et al. (2006). Immunization with the iron uptake ABC transporter proteins PiaA and PiuA prevents respiratory infection with Streptococcus pneumoniae. Vaccine 24:5133-9
62. Jomaa M, Yuste J, Paton JC, et al. (2005). Antibodies to the iron uptake ABC transporter lipoproteins PiaA and PiuA promote opsonophagocytosis of Streptococcus pneumoniae. Infect Immun 73:6852-9
63. Kamtchoua T, Bologa M, Hopfer R, et al. (2013). Safety and immunogenicity of the pneumococcal pneumolysin Derivative PlyD1 in a single-Antigen protein vaccine candidate in adults. Vaccine 31:327-33
64. Khan MN, Bansal A, Shukla D, et al. (2006). Immunogenicity and protective efficacy of DnaJ (hsp40) of Streptococcus pneumoniae against lethal infection in mice. Vaccine 24:6225-31
65. Khan MN, Pichichero ME. (2012). Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine 30:2900-7
66. Khan MN, Sharma SK, Filkins LM, Pichichero ME. (2012). PcpA of Streptococcus pneumoniae mediates adherence to nasopharyngeal and lung epithelial cells and elicits functional antibodies in humans. Microbes Infect 14:1102-10
67. King SJ, Hippe KR, Weiser JN. (2006). Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae. Mol Microbiol 59:961-74
68. Kirkham LA, Kerr AR, Douce GR, et al. (2006). Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines. Infect Immun 74:586-93
69. Langermann S, Palaszynski SR, Burlein JE, et al. (1994). Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guerin vaccines expressing pneumococcal surface protein A. J Exp Med 180:2277-86
70. Li Y, Wang S, Scarpellini G, et al. (2009). Evaluation of new generation Salmonella enterica serovar Typhimurium vaccines with regulated Delayed attenuation to induce immune responses against PspA. Proc Natl Acad Sci U S A 106:593-8
71. Ling E, Feldman G, Portnoi M, et al. (2004). Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae are antigenic in humans and elicit protective immune responses in the mouse. Clin Exp Immunol 138:290-8
72. Lock RA, Hansman D, Paton JC. (1992). Comparative efficacy of autolysin and pneumolysin as immunogens protecting mice against infection by Streptococcus pneumoniae. Microb Pathog 12:137-43
73. Lock RA, Paton JC, Hansman D. (1988). Comparative efficacy of pneumococcal neuraminidase and pneumolysin as immunogens protective against Streptococcus pneumoniae. Microb Pathog 5: 461-7
74. Long JP, Tong HH, Demaria TF. (2004). Immunization with native or recombinant Streptococcus pneumoniae neuraminidase affords protection in the chinchilla otitis media moDel. Infect Immun 72: 4309-13
75. Lu YJ, Forte S, Thompson CM, et al. (2009). Protection against Pneumococcal colonization and fatal pneumonia by a trivalent conjugate of a fusion protein with the cell wall polysacchariDe. Infect Immun 77:2076-83
76. Lu YJ, Leite L, Goncalves VM, et al. (2010). GMP-graDe pneumococcal whole-cell vaccine injected subcutaneously protects mice from nasopharyngeal colonization and fatal aspiration-sepsis. Vaccine 28: 7468-75
77. Mahdi LK, Wang H, Van Der Hoek MB, et al. (2012). IDentification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice. J Clin Invest 122:2208-20
78. Malley R, AnDerson PW. (2012). Serotype-inDepenDent pneumococcal experimental vaccines that induce cellular as well as humoral immunity. Proc Natl Acad Sci U S A 109:3623-7
79. Malley R, Henneke P, Morse SC, et al. (2003). Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci U S A 100:1966-71
80. Malley R, Lipsitch M, Stack A, et al. (2001). Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci. Infect Immun 69: 4870-3
81. Malley R, Morse SC, Leite LC, et al. (2004). Multiserotype protection of mice against pneumococcal colonization of the nasopharynx and middle ear by killed nonencapsulated cells given intranasally with a nontoxic adjuVant. Infect Immun 72:4290-2
82. Malley R, Trzcinski K, Srivastava A, et al. (2005). CD4 T cells mediate antibody-inDepenDent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci U S A 102:4848-53
83. Manco S, Hernon F, Yesilkaya H, et al. (2006). Pneumococcal neuraminidases A and B both have essential roles during infection of the respiratory tract and sepsis. Infect Immun 74:4014-20
84. Marriott HM, Mitchell TJ, Dockrell DH. (2008). Pneumolysin: a doubleedged sword during the host-pathogen interaction. Curr Mol Med 8: 497-509
85. Mcallister LJ, Tseng HJ, Ogunniyi AD, et al. (2004). Molecular analysis of the psa permease complex of Streptococcus pneumoniae. Mol Microbiol 53:889-901
86. Mccool TL, Cate TR, Moy G, Weiser JN. (2002) the immune response to pneumococcal proteins during experimental human carriage. J Exp Med 195:359-65
87. Medina M, Villena J, Vintini E, et al. (2008). Nasal immunization with Lactococcus lactis expressing the pneumococcal protective protein A induces protective immunity in mice. Infect Immun 76: 2696-705
88. Melin M, Coan P, Hollingshead S. (2012). Development of crossreactive antibodies to the proline-rich region of pneumococcal surface protein A in children. Vaccine 30:7157-60
89. Michon F, Fusco PC, Minetti CA, et al. (1998). Multivalent pneumococcal capsular polysacchariDe conjugate vaccines employing genetically Detoxified pneumolysin as a carrier protein. Vaccine 16: 1732-41
90. Mills MF, Marquart ME, Mcdaniel LS. (2007). Localization of PcsB of Streptococcus pneumoniae and its differential expression in response to stress. J bacteriol 189:4544-6
91. Min X, Zhang X, Wang H, et al. (2012). Protection against pneumococcal infection elicited by immunization with glutamyl tRNA synthetase, polyamine transport protein D and sortase A. Vaccine 30:3624-33
92. Mirza S, Wilson L, Benjamin JR. WH, et al. (2011). Serine protease PrtA from Streptococcus pneumoniae plays a role in the killing of S. pneumoniae by apolactoferrin. Infect Immun 79:2440-50
93. Miyaji EN, Dias WO, Gamberini M, et al. (2001). PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae. Vaccine 20:805-12
94. Moffitt KL, Malley R. (2011). Next generation pneumococcal vaccines. Curr Opin Immunol 23:407-13
95. Moffitt KL, Yadav P, Weinberger DM, et al. (2012). Broad antibody and T cell reactivity induced by a pneumococcal whole-cell vaccine. Vaccine 30:4316-22
96. Moreno AT, Oliveira ML, Ferreira DM, et al. (2010). Immunization of mice with single PspA fragments induces antibodies capable of mediating complement Deposition on different pneumococcal strains and cross-protection. Clin Vaccine Immunol 17:439-46
97. Morsczeck C, Prokhorova T, Sigh J, et al. (2008). Streptococcus pneumoniae: proteomics of surface proteins for vaccine Development. Clin Microbiol Infect 14:74-81
98. Mukerji R, Mirza S, Roche AM, et al. (2012). Pneumococcal surface protein a inhibits complement Deposition on the pneumococcal surface by competing with the binding of C-reactive protein to cellsurface phosphocholine. J Immunol 189:5327-35
99. Nabors GS, Braun PA, Herrmann DJ, et al. (2000). Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules. Vaccine 18:1743-54
100. Nguyen CT, Kim SY, Kim MS, et al. (2011). Intranasal immunization with recombinant PspA fused with a flagellin enhances crossprotective immunity against Streptococcus pneumoniae infection in mice. Vaccine 29:5731-9
101. Ochs MM, Bartlett W, Briles DE, et al. (2008). Vaccine-induced human antibodies to PspA augment complement C3 Deposition on Streptococcus pneumoniae. Microb Pathog 44:204-14
102. Ogunniyi AD, Folland RL, Briles DE, et al. (2000). Immunization of mice with combinations of pneumococcal virulence proteins elicits enhanced protection against challenge with Streptococcus pneumoniae. Infect Immun 68:3028-33
103. Ogunniyi AD, Grabowicz M, Briles DE, et al. (2007). Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae. Infect Immun 75: 350-7
104. Ogunniyi AD, Grabowicz M, Mahdi LK, et al. (2009). Pneumococcal histidine triad proteins are regulated by the Zn2-DepenDent repressor AdcR and inhibit complement Deposition through the recruitment of complement factor H. FASEB J 23:731-8
105. Ogunniyi AD, Mahdi LK, Trappetti C, et al. (2012). IDentification of genes that contribute to the pathogenesis of invasive pneumococcal disease by in vivo transcriptomic analysis. Infect Immun 80: 3268-78
106. Ogunniyi AD, Woodrow MC, Poolman JT, Paton JC. (2001). Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA. Infect Immun 69:5997-6003
107. Olafsdottir TA, Lingnau K, Nagy E, Jonsdottir I. (2012). Novel proteinbased pneumococcal vaccines administered with the Th1-promoting adjuVant IC31 induce protective immunity against pneumococcal disease in neonatal mice. Infect Immun 80:461-8
108. Oliveira ML, Areas AP, Campos IB, et al. (2006). Induction of systemic and mucosal immune response and Decrease in Streptococcus pneumoniae colonization by nasal inoculation of mice with recombinant lactic acid bacteria expressing pneumococcal surface antigen A. Microbes Infect 8:1016-24
109. Oliveira ML, Miyaji EN, Ferreira DM, et al. (2010). Combination of pneumococcal surface protein A (PspA) with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice. PLoS One 5:e10863
110. Overweg K, Pericone CD, Verhoef GG, et al. (2000). Differential protein expression in phenotypic variants of Streptococcus pneumoniae. Infect Immun 68:4604-10
111. Paterson GK, Mitchell TJ. (2006) the role of Streptococcus pneumoniae sortase A in colonisation and pathogenesis. Microbes Infect 8:145-53
112. Paton JC. (1996) the contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae. Trends Microbiol 4:103-6
113. Paton JC. (2011). Vaccines against Streptococcus pneumoniae. In: Rappuoli R, Bagnoli F, ed. Vaccine Design-Innovative approache and Novel Strategies. Caister AcaDemic Press: Norfolk, UK, 303-28
114. Paton JC, Lock RA, Lee CJ, et al. (1991). Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to Streptococcus pneumoniae type 19F polysacchariDe. Infect Immun 59:2297-304
115. Perciani CT, Barazzone GC, Goulart C, et al. (2013). Conjugation of PolysacchariDe 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA conformation and its effect on the immune response. Clin Vaccine Immunol 6:858-66
116. Pimenta FC, Miyaji EN, Areas AP, et al. (2006). Intranasal immunization with the cholera toxin B subunit-pneumococcal surface antigen A fusion protein induces protection against colonization with Streptococcus pneumoniae and has negligible impact on the nasopharyngeal and oral microbiota of mice. Infect Immun 74:4939-44
117. Polissi A, Pontiggia A, Feger G, et al. (1998). Large-scale iDentification of virulence genes from Streptococcus pneumoniae. Infect Immun 66: 5620-9
118. Rapola S, Jantti V, Haikala R, et al. (2000). Natural Development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media. J Infect Dis 182:1146-52
119. Ren B, Li J, Genschmer K, et al. (2012) the absence of PspA or presence of antibody to PspA facilitates the complement-DepenDent phagocytosis of pneumococci in vitro. Clin Vaccine Immunol 19: 1574-82
120. Rioux S, Neyt C, DI Paolo E, et al. (2011). Transcriptional regulation, occurrence and putative role of the PhT family of Streptococcus pneumoniae. Microbiology 157:336-48
121. Roche H, Hakansson A, Hollingshead SK, Briles DE. (2003). Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection moDel. Infect Immun 71:1033-41
122. Salha D, Szeto J, Myers L, et al. (2012). Neutralizing antibodies elicited by a novel Detoxified pneumolysin Derivative, PlyD1, proviDe protection against both pneumococcal infection and lung injury. Infect Immun 80:2212-20
123. Sanchez-Beato AR, Lopez R, Garcia JL. (1998). Molecular characterization of PcpA: a novel choline-binding protein of Streptococcus pneumoniae. FEMS Microbiol Lett 164:207-14
124. Santamaria R, Goulart C, Perciani CT, et al. (2011). Humoral immune response of a pneumococcal conjugate vaccine: capsular polysacchariDe serotype 14-Lysine modified PspA. Vaccine 29:8689-95
125. Santolaya ME, Oryan ML, Valenzuela MT, et al. (2012). Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet 379:617-24
126. Saskova L, Novakova L, Basler M, Branny P. (2007). Eukaryotic-type serine/threonine protein kinase StkP is a global regulator of gene expression in Streptococcus pneumoniae. J Bacteriol 189:4168-79
127. Seepersaud R, Hanniffy SB, Mayne P, et al. (2005). Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity. Infec Immun 73:1671-83
128. Seiberling M, Bologa M, Brookes R, et al. (2012). Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults. Vaccine 30:7455-60
129. Selva L, Ciruela P, Blanchette K, et al. (2012). Prevalence and clonal distribution of PcpA, PsrP and Pilus-1 among pediatric isolates of Streptococcus pneumoniae. PLoS One 7:e41587
130. Shah P, Marquart M, Quin LR, Swiatlo E. (2006). Cellular location of polyamine transport protein PotD in Streptococcus pneumoniae. FEMS Microbiol Lett 261:235-7
131. Shah P, Romero DG, Swiatlo E. (2008). Role of polyamine transport in Streptococcus pneumoniae response to physiological stress and murine septicemia. Microbial Pathogen 45:167-72
132. Shah P, Swiatlo E. (2006). Immunization with polyamine transport protein PotD protects mice against systemic infection with Streptococcus pneumoniae. Infec Immun 74:5888-92
133. Shaper M, Hollingshead SK, Benjamin JR WH, Briles DE. (2004). PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin [corrected]. Infect Immun 72:5031-40
134. Shi H, Wang S, Roland KL, et al. (2010). Immunogenicity of a live recombinant Salmonella enterica serovar typhimurium vaccine expressing pspA in neonates and infant mice born from naive and immunized mothers. Clin Vaccine Immunol 17:363-71
135. Spraggon G, Koesema E, Scarselli M, et al. (2010). Supramolecular organization of the repetitive backbone unit of the Streptococcus pneumoniae pilus. PLoS One 5:e10919
136. Talkington DF, Brown BG, Tharpe JA, et al. (1996). Protection of mice against fatal pneumococcal challenge by immunization with pneumococcal surface adhesin A (PsaA). Microb Pathog 21:17-22
137. Tettelin H, Nelson KE, Paulsen IT, et al. (2001). Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293:498-506
138. Tong HH, Li D, Chen S, et al. (2005). Immunization with recombinant Streptococcus pneumoniae neuraminidase NanA protects chinchillas against nasopharyngeal colonization. Infect Immun 73:7775-8
139. Tseng HJ, Mcewan AG, Paton JC, Jennings MP. (2002). Virulence of Streptococcus pneumoniae: PsaA mutants are hypersensitive to oxidative stress. Infect Immun 70:1635-9
140. Vela Coral MC, Fonseca N, Castaneda E, et al. (2001). Pneumococcal surface protein A of invasive Streptococcus pneumoniae isolates from Colombian children. Emerg Infect Dis 7:832-6
141. Vintini E, Villena J, Alvarez S, Medina M. (2010). Administration of a probiotic associated with nasal vaccination with inactivated Lactococcus lactis-PppA induces effective protection against pneumoccocal infection in young mice. Clin Exp Immunol 159: 351-62
142. Virolainen A, Russell W, Crain MJ, et al. (2000). Human antibodies to pneumococcal surface protein A in health and disease. Pediatr Infect Dis J 19:134-8
143. Wang S, Li Y, Shi H, et al. (2010). Immune responses to recombinant pneumococcal PsaA antigen Delivered by a live attenuated Salmonella vaccine. Infect Immun 78:3258-71
144. Ware D, Watt J, Swiatlo E. (2005). Utilization of putrescine by Streptococcus pneumoniae during growth in choline-limited medium. J Microbiol 43:398-405
145. Weinberger DM, Malley R, Lipsitch M. (2011). Serotype replacement in disease after pneumococcal vaccination. Lancet 378:1962-73
146. Whalan RH, Funnell SG, Bowler LD, et al. (2005). PiuA and Piaa, iron uptake lipoproteins of Streptococcus pneumoniae, elicit serotype inDepenDent antibody responses following human pneumococcal septicaemia. FEMS Immunol Med Microbiol 43:73-80
147. WHO. (2006). State of the art of new vaccine and Development. Immunization, Vaccines and Biologicals Available from: whqlibdoc
148. who.int/hq/2006/who-ivb-06.01-eng.pdf [Last accessed 6 May 2013]
149. Weiser NJ. (2010) the pneumococcus: why a commensal misbehaves. J Mol Med 88:97-102
150. Whaley MJ, Sampson JS, Johnson SE, et al. (2010). Concomitant administration of recombinant PsaA and PCV7 reduces Streptococcus pneumoniae serotype 19A colonization in a murine moDel. Vaccine 28:3071-5
151. Witzenrath M, Pache F, Lorenz D, et al. (2011) the NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host Defense in pneumococcal pneumonia. J Immunol 187:434-40
152. Wizemann TM, Heinrichs JH, Adamou JE, et al. (2001). Use of a whole genome approach to iDentify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect Immun 69: 1593-8
153. Wright AK, Ferreira DM, Gritzfeld JF, et al. (2012). Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage. PLoS pathogens 8:e1002622
154. Wu K, Zhang X, Shi J, et al. (2010). Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae Infections in Mice. Infect Immun 78:1276-83
155. Yuan ZQ, Lv ZY, Gan HQ, et al. (2011). Intranasal immunization with autolysin (LytA) in mice moDel induced protection against five prevalent Streptococcus pneumoniae serotypes in China. Immunol Res 51:108-15
156. Zhang Y, Masi AW, Barniak V, et al. (2001). Recombinant PhpA protein, a unique histidine motif-containing protein from Streptococcus pneumoniae, protects mice against intranasal pneumococcal challenge. Infect Immun 69:3827-36
157. Zhong W, Xu W, Wang H, et al. (2012). Mucosal immunization with caseinolytic protease X elicited cross-protective immunity against pneumococcal infection in mice. Exp Biol Med (Maywood) 237: 694-702