2,082
Views
42
CrossRef citations to date
0
Altmetric
Review

Rationale and prospects for novel pneumococcal vaccines

&
Pages 383-392 | Received 08 Jun 2015, Accepted 22 Aug 2015, Published online: 23 Feb 2016

References

  • Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O'Brien KL, Campbell H, Black RE. Global burden of childhood pneumonia and diarrhoea. Lancet 2013; 381(9875):1405-16; PMID:23582727; http://dx.doi.org/10.1016/S0140-6736(13)60222-6
  • O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, Lee E, Mulholland K, Levine OS, Cherian T. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 2009; 374(9693):893-902; PMID:19748398; http://dx.doi.org/10.1016/S0140-6736(09)61204-6
  • Davis SM, Deloria-Knoll M, Kassa HT, O'Brien KL. Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: review of evidence on indirect effects. Vaccine 2013; 32(1):133-45; PMID:23684824; http://dx.doi.org/10.1016/j.vaccine.2013.05.005
  • Loo JD, Conklin L, Fleming-Dutra KE, Knoll MD, Park DE, Kirk J, Goldblatt D, O'Brien KL, Whitney CG. Systematic review of the indirect effect of pneumococcal conjugate vaccine dosing schedules on pneumococcal disease and colonization. Pediatr Infect Dis J 2014; 33 Suppl 2:S161-71; PMID:24336058; http://dx.doi.org/10.1097/INF.0000000000000084
  • Harboe ZB, Dalby T, Weinberger DM, Benfield T, Molbak K, Slotved HC, Suppli CH, Konradsen HB, Valentiner-Branth P. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality. Clin Infect Dis 2014; 59(8):1066-73; PMID:25034421; http://dx.doi.org/10.1093/cid/ciu524
  • Auranen K, Rinta-Kokko H, Goldblatt D, Nohynek H, O'Brien KL, Satzke C, Simell B, Tanskanen A, Käyhty H. Colonisation endpoints in Streptococcus pneumoniae vaccine trials. Vaccine 2013; 32(1):153-8; PMID:24016803; http://dx.doi.org/10.1016/j.vaccine.2013.08.061
  • Goldblatt D, Ramakrishnan M, O'Brien K. Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation; a PneumoCarr meeting report March 27-28, 2012, Geneva. Vaccine 2013; 32(1):146-52; PMID:23933374; http://dx.doi.org/10.1016/j.vaccine.2013.06.040
  • Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, Levine OS, Whitney CG, O'Brien KL, Moore MR. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 2013; 10(9):e1001517; http://dx.doi.org/10.1371/journal.pmed.1001517
  • Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infectious Dis 2011; 11(10):760-8; http://dx.doi.org/10.1016/S1473-3099(11)70090-1
  • Tocheva AS, Jefferies JM, Christodoulides M, Faust SN, Clarke SC. Distribution of carried pneumococcal clones in UK children following the introduction of the 7-valent pneumococcal conjugate vaccine: a 3-year cross-sectional population based analysis. Vaccine 2013; 31(31):3187-90; PMID:23680442; http://dx.doi.org/10.1016/j.vaccine.2013.04.075
  • Tocheva AS, Jefferies JM, Rubery H, Bennett J, Afimeke G, Garland J, Christodoulides M, Faust SN, Clarke SC. Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children. Vaccine 2011; 29(26):4400-4; PMID:21504773; http://dx.doi.org/10.1016/j.vaccine.2011.04.004
  • Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet 2011; 378(9807):1962-73; PMID:21492929; http://dx.doi.org/10.1016/S0140-6736(10)62225-8
  • Lipsitch M. Vaccination against colonizing bacteria with multiple serotypes. Proc Natl Acad Sci U S A 1997; 94(12):6571-6; PMID:9177259; http://dx.doi.org/10.1073/pnas.94.12.6571
  • Progress in introduction of pneumococcal conjugate vaccine- worldwide, 2000-2012. MMWR Morb Mortal Wkly Rep 2013 Apr 26: Centers for Disease Control and Prevention (CDC)
  • Rapola S, Jantti V, Haikala R, Syrjanen R, Carlone GM, Sampson JS, Briles DE, Paton JC, Takala AK, Kilpi TM, et al. 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 2000; 182(4):1146-52; PMID:10979911; http://dx.doi.org/10.1086/315822
  • Holmlund E, Quiambao B, Ollgren J, Nohynek H, Kayhty H. Development of natural antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A and pneumolysin in Filipino pregnant women and their infants in relation to pneumococcal carriage. Vaccine 2006; 24(1):57-65; PMID:16115703; http://dx.doi.org/10.1016/j.vaccine.2005.07.055
  • Laine C, Mwangi T, Thompson CM, Obiero J, Lipsitch M, Scott JA. Age-specific immunoglobulin g (IgG) and IgA to pneumococcal protein antigens in a population in coastal kenya. Infect Immun 2004; 72(6):3331-5; PMID:15155637; http://dx.doi.org/10.1128/IAI.72.6.3331-3335.2004
  • Anderson P. Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197. Infect Immun 1983; 39(1):233-8; PMID:6600444
  • Anderson P, Pichichero ME, Insel RA. Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b. J Pediatr 1985; 107(3):346-51; PMID:3875705; http://dx.doi.org/10.1016/S0022-3476(85)80504-7
  • Anderson P, Pichichero ME, Insel RA. Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197. J Clin Invest 1985; 76(1):52-9; PMID:3874882; http://dx.doi.org/10.1172/JCI111976
  • Anderson PW, Pichichero ME, Insel RA, Betts R, Eby R, Smith DH. Vaccines consisting of periodate-cleaved oligosaccharides from the capsule of Haemophilus influenzae type b coupled to a protein carrier: structural and temporal requirements for priming in the human infant. J Immunol 1986; 137(4):1181-6; PMID:3016088
  • Jakobsen H, Hannesdottir S, Bjarnarson SP, Schulz D, Trannoy E, Siegrist CA, Jonsdottir I. Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide-specific antibody response and protective efficacy. Eur J Immunol 2006; 36(2):287-95; PMID:16385627; http://dx.doi.org/10.1002/eji.200535102
  • Clarke ET, Williams NA, Findlow J, Borrow R, Heyderman RS, Finn A. Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells. J Immunol 2013; 191(12):6071-83; PMID:24227777; http://dx.doi.org/10.4049/jimmunol.1203254
  • Siber GR, Chang I, Baker S, Fernsten P, O'Brien KL, Santosham M, Klugman KP, Madhi SA, Paradiso P, Kohberger R. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine 2007; 25(19):3816-26; PMID:17368878; http://dx.doi.org/10.1016/j.vaccine.2007.01.119
  • Romero-Steiner S, Libutti D, Pais LB, Dykes J, Anderson P, Whitin JC, Keyserling HL, Carlone GM. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin Diagn Lab Immunol 1997; 4(4):415-22; PMID:9220157
  • Juergens C, Patterson S, Trammel J, Greenberg D, Givon-Lavi N, Cooper D, Gurtman A, Gruber WC, Scott DA, Dagan R. Post hoc analysis of a randomized double-blind trial of the correlation of functional and binding antibody responses elicited by 13-valent and 7-valent pneumococcal conjugate vaccines and association with nasopharyngeal colonization. Clin Vaccine Immunol 2014; 21(9):1277-81; PMID:24990907; http://dx.doi.org/10.1128/CVI.00172-14
  • Dagan R, Patterson S, Juergens C, Greenberg D, Givon-Lavi N, Porat N, Gurtman A, Gruber WC, Scott DA. Comparative immunogenicity and efficacy of 13-valent and 7-valent pneumococcal conjugate vaccines in reducing nasopharyngeal colonization: a randomized double-blind trial. Clin Infect Dis 2013; 57(7):952-62; PMID:23804191; http://dx.doi.org/10.1093/cid/cit428
  • Austrian R. Pneumococcal infections. In: Germanier R, editor. Bacterial Vaccines. Orlando FL: Academic Press; 1984. p. 257-88
  • Lipsitch M, Whitney CG, Zell E, Kaijalainen T, Dagan R, Malley R. Age-specific incidence of invasive pneumococcal disease by serotype: Are anticapsular antibodies the primary mechanism of protection against invasive disease? PLoS Med 2005; 2(1):e15; PMID:15696204; http://dx.doi.org/10.1371/journal.pmed.0020015
  • Croucher NJ, Chewapreecha C, Hanage WP, Harris SR, McGee L, van der Linden M, Song JH, Ko KS, de Lencastre H, Turner C, et al. Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape. Genome Biol Evol 2014; 6(7):1589-602; PMID:24916661; http://dx.doi.org/10.1093/gbe/evu120
  • Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J, van der Linden M, McGee L, von Gottberg A, Song JH, Ko KS. Rapid pneumococcal evolution in response to clinical interventions. Science 2011; 331(6016):430-4; PMID:21273480; http://dx.doi.org/10.1126/science.1198545
  • Gaschignard J, Levy C, Chrabieh M, Boisson B, Bost-Bru C, Dauger S, Dubos F, Durand P, Gaudelus J, Gendrel D, et al. Invasive pneumococcal disease in children can reveal a primary immunodeficiency. Clin Infect Dis 2014; 59(2):244-51; http://dx.doi.org/10.1093/cid/ciu274
  • Dworkin MS, Ward JW, Hanson DL, Jones JL, Kaplan JE. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis 2001; 32(5):794-800; PMID:11229848; http://dx.doi.org/10.1086/319218
  • Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, Takala A, Käyhty H, Karma P, Kohberger R, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001; 344(6):403-9; PMID:11172176; http://dx.doi.org/10.1056/NEJM200102083440602
  • Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, Elvin L, Ensor KM, Hackell J, Siber G, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J 2000; 19(3):187-95
  • Lucero MG, Dulalia VE, Nillos LT, Williams G, Parreno RA, Nohynek H, Riley ID, Makela H. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev 2009(4):CD004977; PMID:19821336
  • Lucero MG, Nohynek H, Williams G, Tallo V, Simoes EA, Lupisan S, Sanvictores D, Forsyth S, Puumalainen T, Ugpo J, et al. Efficacy of an 11-valent pneumococcal conjugate vaccine against radiologically confirmed pneumonia among children less than 2 years of age in the Philippines: a randomized, double-blind, placebo-controlled trial. Pediatr Infect Dis J 2009; 28(6):455-62; PMID:19483514; http://dx.doi.org/10.1097/INF.0b013e31819637af
  • Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, van Werkhoven CH, van Deursen AM, Sanders EA, Verheij TJ, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372(12):1114-25; PMID:25785969; http://dx.doi.org/10.1056/NEJMoa1408544
  • Weinberger DM, Bruhn CA, Shapiro ED. Vaccine against Pneumococcal Pneumonia in Adults. N Engl J Med 2015; 373(1):92; PMID:26132955
  • Swartz AW. Vaccine against Pneumococcal Pneumonia in Adults. N Engl J Med 2015; 373(1):91-2; PMID:26132953; http://dx.doi.org/10.1056/NEJMc1505366
  • Weinberger DM, Shapiro ED. Pneumococcal conjugate vaccines for adults: reasons for optimism and for caution. Hum Vaccin Immunother 2014; 10(5):1334-6; PMID:24763136; http://dx.doi.org/10.4161/hv.28962
  • Fireman B, Black SB, Shinefield HR, Lee J, Lewis E, Ray P. Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J 2003; 22(1):10-6; PMID:12544402; http://dx.doi.org/10.1097/00006454-200301000-00006
  • Kilpi T, Ahman H, Jokinen J, Lankinen KS, Palmu A, Savolainen H, Grönholm M, Leinonen M, Hovi T, Eskola J, et al. Protective efficacy of a second pneumococcal conjugate vaccine against pneumococcal acute otitis media in infants and children: randomized, controlled trial of a 7-valent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine in 1666 children. Clin Infect Dis 2003; 37(9):1155-64; PMID:14557958; http://dx.doi.org/10.1086/378744
  • Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, Kohl I, Lommel P, Poolman J, Prieels JP, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 2006; 367(9512):740-8; PMID:16517274; http://dx.doi.org/10.1016/S0140-6736(06)68304-9
  • Rapola S, Kilpi T, Lahdenkari M, Makela PH, Kayhty H. Antibody response to the pneumococcal proteins pneumococcal surface adhesin A and pneumolysin in children with acute otitis media. Pediatr Infect Dis J 2001; 20(5):482-7; PMID:11368104; http://dx.doi.org/10.1097/00006454-200105000-00003
  • Xu Q, Casey JR, Pichichero ME. Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children. Mucosal Immunol 2015; 8(5):1110-7: e1-8
  • Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, Thumerelle C, Oksenhendler E, Boutboul D, Thomas C, et al. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine (Baltimore) 2012; 91(4):e1-19; PMID:22751495; http://dx.doi.org/10.1097/MD.0b013e31825f95b9
  • Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 2008; 452(7188):773-6; PMID:18337720; http://dx.doi.org/10.1038/nature06764
  • Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, Fulcher DA, Tangye SG, Cook MC. Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 2008; 205(7):1551-7; http://dx.doi.org/10.1084/jem.20080218
  • Khader SA, Gaffen SL, Kolls JK. Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol 2009; 2(5):403-11; http://dx.doi.org/10.1038/mi.2009.100
  • Kolls JK, Khader SA. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev 2010; 21(6):443-8; PMID:21095154; http://dx.doi.org/10.1016/j.cytogfr.2010.11.002
  • Khan MN, Pichichero ME. The host immune dynamics of pneumococcal colonization: implications for novel vaccine development. Hum Vaccin Immunother 2014; 10(12):3688-99; PMID:25668673; http://dx.doi.org/10.4161/21645515.2014.979631
  • Ferreira DM, Neill DR, Bangert M, Gritzfeld JF, Green N, Wright AK, Pennington SH, Bricio-Moreno L, Moreno AT, Miyaji EN, et al. Controlled human infection and rechallenge with Streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults. Am J Respir Crit Care Med 2013; 187(8):855-64; PMID:23370916; http://dx.doi.org/10.1164/rccm.201212-2277OC
  • Wright AK, Ferreira DM, Gritzfeld JF, Wright AD, Armitage K, Jambo KC, Bate E, El Batrawy S, Collins A, Gordon F. Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage. PLoS Pathog 2012; 8(4):e1002622; PMID:22496648; http://dx.doi.org/10.1371/journal.ppat.1002622
  • McCool TL, Weiser JN. Limited Role of Antibody in Clearance of Streptococcus pneumoniae in a Murine Model of Colonization. Infect Immun 2004; 72(10):5807-13; PMID:15385481; http://dx.doi.org/10.1128/IAI.72.10.5807-5813.2004
  • van Rossum AM, Lysenko ES, Weiser JN. Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model. Infect Immun 2005; 73(11):7718-26; PMID:16239576; http://dx.doi.org/10.1128/IAI.73.11.7718-7726.2005
  • Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, et al. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog. 2008; 4(9):e1000159; PMID:18802458; http://dx.doi.org/10.1371/journal.ppat.1000159
  • Trzcinski K, Thompson CM, Srivastava A, Basset A, Malley R, Lipsitch M. Protection against Nasopharyngeal Colonization by Streptococcus pneumoniae is Mediated by Antigen-Specific CD4+ T Cells. Infect Immun 2008; 76(6):2678-84; PMID:18391006; http://dx.doi.org/10.1128/IAI.00141-08
  • Zhang Z, Clarke TB, Weiser JN. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 2009; 119(7):1899-909; PMID:19509469
  • Lu YJ, Skovsted IC, Thompson CM, Anderson PW, Malley R. Mechanisms in the serotype-independent pneumococcal immunity induced in mice by intranasal vaccination with the cell wall polysaccharide. Microb Pathog 2009; 47(3):177-82; PMID:19577628; http://dx.doi.org/10.1016/j.micpath.2009.06.008
  • Moffitt KL, Gierahn TM, Lu YJ, Gouveia P, Alderson M, Flechtner JB, Higgins DE, Malley R. T(H)17-Based Vaccine Design for Prevention of Streptococcus pneumoniae Colonization. Cell Host Microbe 2011; 9(2):158-65; PMID:21320698; http://dx.doi.org/10.1016/j.chom.2011.01.007
  • Feldman C, Anderson R. Review: current and new generation pneumococcal vaccines. J Infect 2014; 69(4):309-25; PMID:24968238; http://dx.doi.org/10.1016/j.jinf.2014.06.006
  • Moffitt KL, Malley R. Next generation pneumococcal vaccines. Curr Opin Immunol 2011; 23(3):407-13; PMID:21514128; http://dx.doi.org/10.1016/j.coi.2011.04.002
  • Miyaji EN, Oliveira ML, Carvalho E, Ho PL. Serotype-independent pneumococcal vaccines. Cell Mol Life Sci 2013; 70(18):3303-26; PMID:23269437; http://dx.doi.org/10.1007/s00018-012-1234-8
  • Darrieux M, Goulart C, Briles D, Leite LC. Current status and perspectives on protein-based pneumococcal vaccines. Crit Rev Microbiol 2015; 41(2):190-200; PMID:23895377; http://dx.doi.org/10.3109/1040841X.2013.813902
  • Ren B, Li J, Genschmer K, Hollingshead SK, Briles DE. The absence of PspA or presence of antibody to PspA facilitates the complement-dependent phagocytosis of pneumococci in vitro. Clin Vaccine Immunol 2012; 19(10):1574-82; PMID:22855389; http://dx.doi.org/10.1128/CVI.00393-12
  • Ren B, Szalai AJ, Hollingshead SK, Briles DE. Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surface. Infect Immun 2004; 72(1):114-22; PMID:14688088; http://dx.doi.org/10.1128/IAI.72.1.114-122.2004
  • Ren B, Szalai AJ, Thomas O, Hollingshead SK, Briles DE. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect Immun 2003; 71(1):75-85; PMID:12496151; http://dx.doi.org/10.1128/IAI.71.1.75-85.2003
  • Wu HY, Nahm MH, Guo Y, Russell MW, Briles DE. Intranasal immunization of mice with PspA (pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae. J Infect Dis 1997; 175(4):839-46; PMID:9086139; http://dx.doi.org/10.1086/513980
  • McCool TL, Cate TR, Tuomanen EI, Adrian P, Mitchell TJ, Weiser JN. Serum immunoglobulin G response to candidate vaccine antigens during experimental human pneumococcal colonization. Infect Immun 2003; 71(10):5724-32; PMID:14500493; http://dx.doi.org/10.1128/IAI.71.10.5724-5732.2003
  • Nabors GS, Braun PA, Herrmann DJ, Heise ML, Pyle DJ, Gravenstein S, Schilling M, Ferguson LM, Hollingshead SK, Briles DE, et al. Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules. Vaccine 2000; 18(17):1743-54; PMID:10699322; http://dx.doi.org/10.1016/S0264-410X(99)00530-7
  • Briles DE, Hollingshead SK, King J, Swift A, Braun PA, Park MK, Ferguson LM, Nahm MH, Nabors GS. 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 2000; 182(6):1694-701; PMID:11069242; http://dx.doi.org/10.1086/317602
  • Ginsburg AS, Nahm MH, Khambaty FM, Alderson MR. Issues and challenges in the development of pneumococcal protein vaccines. Expert Rev Vaccines 2012; 11(3):279-85; PMID:22380821; http://dx.doi.org/10.1586/erv.12.5
  • Alexander JE, Lock RA, Peeters CC, Poolman JT, Andrew PW, Mitchell TJ, Hansman D, Paton JC. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect Immun 1994; 62(12):5683-8; PMID:7960154
  • Francis JP, Richmond PC, Pomat WS, Michael A, Keno H, Phuanukoonnon S, Nelson JB, Whinnen M, Heinrich T, Smith F, et al. Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants. Clin Vaccine Immunol 2009; 16(11):1633-8; http://dx.doi.org/10.1128/CVI.00247-09
  • Kaur R, Surendran N, Ochs M, Pichichero ME. Human antibodies to PhtD, PcpA, and Ply reduce adherence to human lung epithelial cells and murine nasopharyngeal colonization by Streptococcus pneumoniae. Infect Immun 2014; 82(12):5069-75; PMID:25245804; http://dx.doi.org/10.1128/IAI.02124-14
  • Walker JA, Allen RL, Falmagne P, Johnson MK, Boulnois GJ. Molecular cloning, characterization, and complete nucleotide sequence of the gene for pneumolysin, the sulfhydryl-activated toxin of Streptococcus pneumoniae. Infect Immun 1987; 55(5):1184-9; PMID:3552992
  • Kamtchoua T, Bologa M, Hopfer R, Neveu D, Hu B, Sheng X, Corde N, Pouzet C, Zimmermann G, Gurunathan S. Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a single-antigen protein vaccine candidate in adults. Vaccine. 2013; 31(2):327-33; PMID:23153437; http://dx.doi.org/10.1016/j.vaccine.2012.11.005
  • Wizemann TM, Heinrichs JH, Adamou JE, Erwin AL, Kunsch C, Choi GH, Barash SC, Rosen CA, Masure HR, Tuomanen E, et al. Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect Immun 2001; 69(3):1593-8; PMID:11179332; http://dx.doi.org/10.1128/IAI.69.3.1593-1598.2001
  • Adamou JE, Heinrichs JH, Erwin AL, Walsh W, Gayle T, Dormitzer M, Dagan R, Brewah YA, Barren P, Lathigra R, et al. Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis. Infect Immun 2001; 69(2):949-58; PMID:11159990; http://dx.doi.org/10.1128/IAI.69.2.949-958.2001
  • Godfroid F, Hermand P, Verlant V, Denoel P, Poolman JT. Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infect Immun 2011; 79(1):238-45; PMID:20956575; http://dx.doi.org/10.1128/IAI.00378-10
  • Khan MN, Pichichero ME. Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine 2012; 30(18):2900-7; PMID:22349524; http://dx.doi.org/10.1016/j.vaccine.2012.02.023
  • Khan MN, Pichichero ME. CD4 T cell memory and antibody responses directed against the pneumococcal histidine triad proteins PhtD and PhtE following nasopharyngeal colonization and immunization and their role in protection against pneumococcal colonization in mice. Infect Immun 2013; 81(10):3781-92; PMID:23897609; http://dx.doi.org/10.1128/IAI.00313-13
  • Odutola A, Ota MO, Antonia M, Ogundarw OE, Owiafe P, Worwui A, Greenwood B, Alderson M, Traskine M, Dobbelaere K, et al, editor. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: phase II randomized study. ISPPD-Abstract 0407 2014; Hyderabad, India
  • Prymula R, Szenborn L, Silfverdal SA, Wysocki J, Albrecht P, Francois N, Gardev A, Borys D, editor. Immunogenicity of primary vaccination with an investigational protein-based pneumococcal vaccine in infants in Europe: a phase II randomized trial. ISPPD-Abstract 0551 2014; Hyderabad, India
  • Chang L, Brooks WA, deBruyn G, Bologa M, Hopfer R, Kriby D¸ Sheng X, Neveu D, Menezes J, Ochs M, et al, editor. A multi-component pneumococcal protein vaccine is safe and immunogenic in a phase I randomized, placebo-controlled study. ISPPD- Abstract 0542 2014; Hyderabad, India
  • Khan MN, Sharma SK, Filkins LM, Pichichero ME. PcpA of Streptococcus pneumoniae mediates adherence to nasopharyngeal and lung epithelial cells and elicits functional antibodies in humans. Microbes Infect 2012; 14(12):1102-10; PMID:22796387; http://dx.doi.org/10.1016/j.micinf.2012.06.007
  • Glover DT, Hollingshead SK, Briles DE. Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infect Immun 2008; 76(6):2767-76; PMID:18391008; http://dx.doi.org/10.1128/IAI.01126-07
  • Bologa M, Kamtchoua T, Hopfer R, Sheng X, Hicks B, Bixler G, Hou V, Pehlic V, Yuan T, Gurunathan S. Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine triad protein D vaccine. Vaccine 2012; 30(52):7461-8; PMID:23123106; http://dx.doi.org/10.1016/j.vaccine.2012.10.076
  • Talkington DF, Brown BG, Tharpe JA, Koenig A, Russell H. Protection of mice against fatal pneumococcal challenge by immunization with pneumococcal surface adhesin A (PsaA). Microb Pathog 1996; 21(1):17-22; PMID:8827703; http://dx.doi.org/10.1006/mpat.1996.0038
  • Whaley MJ, Sampson JS, Johnson SE, Rajam G, Stinson-Parks A, Holder P, Mauro E, Romero-Steiner S, Carlone GM, Ades EW. Concomitant administration of recombinant PsaA and PCV7 reduces Streptococcus pneumoniae serotype 19A colonization in a murine model. Vaccine 2010; 28(18):3071-5; PMID:20206671; http://dx.doi.org/10.1016/j.vaccine.2010.02.086
  • Briles DE, Ades E, Paton JC, Sampson JS, Carlone GM, Huebner RC, Virolainen A, Swiatlo E, Hollingshead SK. 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 2000; 68(2):796-800; PMID:10639448; http://dx.doi.org/10.1128/IAI.68.2.796-800.2000
  • Giefing C, Meinke AL, Hanner M, Henics T, Bui MD, Gelbmann D, Lundberg U, Senn BM, Schunn M, Habel A, et al. Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J Exp Med 2008; 205(1):117-31; PMID:18166586; http://dx.doi.org/10.1084/jem.20071168
  • Schmid P, Selak S, Keller M, Luhan B, Magyarics Z, Seidel S, Schlick P, Reinisch C, Lingnau K, Nagy E, et al. Th17/Th1 biased immunity to the pneumococcal proteins PcsB, StkP and PsaA in adults of different age. Vaccine 2011; 29(23):3982-9; PMID:21481328; http://dx.doi.org/10.1016/j.vaccine.2011.03.081
  • Nagy E, editor. IC47, a novel protein-based pneumococcal vaccine: from bench to the clinic. ISPPD- Abstract 031 2010; Tel Aviv, Israel
  • Li Y, Gierahn T, Thompson CM, Trzcinski K, Ford CB, Croucher N, Gouveia P, Flechtner JB, Malley R, Lipsitch M, et al. Distinct effects on diversifying selection by two mechanisms of immunity against Streptococcus pneumoniae. PLoS Pathog 2012; 8(11):e1002989; PMID:23144610; http://dx.doi.org/10.1371/journal.ppat.1002989
  • Moffitt K, Skoberne M, Howard A, Gavrilescu LC, Gierahn T, Munzer S, Dixit B, Giannasca P, Flechtner JB, Malley R. Toll-like receptor 2-dependent protection against pneumococcal carriage by immunization with lipidated pneumococcal proteins. Infect Immun 2014; 82(5):2079-86; PMID:24614661; http://dx.doi.org/10.1128/IAI.01632-13
  • Skoberne M MM, Morris A, Hopson K, Chan J, O'Toole M, Velez D, Siddall N, Hart M, Cooney M, Flechtner JB, et al, editor. Safety and immunogenicity of a novel lipidated protein subunit Streptococcus pneumoniae vaccine. Int Conference Antimicrobial Agents Chemotherapy 2014; Washington, DC
  • Xin W, Li Y, Mo H, Roland KL, Curtiss R, 3rd. PspA family fusion proteins delivered by attenuated Salmonella enterica serovar Typhimurium extend and enhance protection against Streptococcus pneumoniae. Infect Immun 2009; 77(10):4518-28; PMID:19687204; http://dx.doi.org/10.1128/IAI.00486-09
  • Frey SE, Lottenbach KR, Hill H, Blevins TP, Yu Y, Zhang Y, Brenneman KE, Kelly-Aehle SM, McDonald C, Jansen A, et al. A Phase I, dose-escalation trial in adults of three recombinant attenuated Salmonella Typhi vaccine vectors producing Streptococcus pneumoniae surface protein antigen PspA. Vaccine 2013; 31(42):4874-80; PMID:23916987; http://dx.doi.org/10.1016/j.vaccine.2013.07.049
  • Makela PH BJ. History of pneumococcal immunization. Siber GR KK, Makela PH. Washington, DC.: ASM Press; 2008
  • Lu YJ, Leite L, Goncalves VM, Dias Wde O, Liberman C, Fratelli F, Alderson M, Tate A, Maisonneuve JF, Robertson G, et al. GMP-grade pneumococcal whole-cell vaccine injected subcutaneously protects mice from nasopharyngeal colonization and fatal aspiration-sepsis. Vaccine 2010; 28(47):7468-75; PMID:20858450; http://dx.doi.org/10.1016/j.vaccine.2010.09.031
  • Lu YJ, Yadav P, Clements JD, Forte S, Srivastava A, Thompson CM, Seid R, Look J, Alderson M, Tate A, et al. Options for inactivation, adjuvant, and route of topical administration of a killed, unencapsulated pneumococcal whole-cell vaccine. Clin Vaccine Immunol 2010; 17(6):1005-12; PMID:20427625; http://dx.doi.org/10.1128/CVI.00036-10
  • Alderson M, Malley R, Anderson P, Thompson C, Morrison R, Briles D, King J, Goldblatt D, Green N, Hural J, et al, editor. A phase 1 study to assess the safety, tolerability and immunogenicity of inactivated non-encapsualted Streptococcus pneumoniae whole cell vaccine. ISPPD- Abstract 0121 2014; Hyderabad, India
  • Briles D, King J, Hale Y, Malley R, Anderson P, Keech C, Tate A, Maisonneuve J, Alderson M. editor. Immune sera from adults immunized with killed whole cell nonencapsulated vaccine protects mice from fatal infection with type 3 pneumococci. ISPPD- Abstract 0122 2104; Hyderabad, India

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.