Abstract
The introduction of Haemophilus influenzae type b (Hib) vaccine into the universal immunisation schedules of many industrialised countries and the subsequent remarkable decline in the incidence of invasive Hib disease has further highlighted the impact of invasive pneumococcal diseases. Streptococcus pneumoniae is now the leading cause of bacterial meningitis in children in many settings and a leading cause of vaccine-preventable bacterial disease in children worldwide.
The currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage at a relatively low cost. However, it is not efficacious in young children. Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive disease in infants and young children, with favourable safety and immunogenicity profiles. These vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e. otitis media), nasopharyngeal acquisition of vaccine-specific serotypes of S. pneumoniae, and protection against pneumococcal disease caused by resistant strains. However, PCV contains a limited number of pneumococcal serotypes and, given adequate ecological pressure, replacement disease by non-vaccine serotypes remains a threat, particularly in areas with very high disease burden. Furthermore, although capsular-specific antibodies have been shown to be highly protective, it remains unclear what concentration of these serotype-specific antibodies protect against disease and, more recently, it has become clear that opsonic activity and avidity of these antibodies are more critical determinants of protection than concentration. Therefore, monitoring disease burden and defining immune correlates of protection after widespread use of conjugate vaccines are crucial for the evaluation of these new generation vaccines. Furthermore, a need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage.
Development of one or more protein vaccines that might be easier and, thus, less expensive to manufacture, and which might provide protection against multiple serotypes, is in progress. This article reviews the current state of pneumococcal disease and pneumococcal vaccines in clinical use.
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References
Peltola H. Burden of meningitis and other severe bacterial infections of children in africa: implications for prevention. Clin Infect Dis 2001; 32: 64–75
Shann F. The management of pneumonia in children in developing countries. Clin Infect Dis 1995; 21 Suppl. 3: S218–25
Douglas RM. Respiratory tract infections as a public health challenge. Clin Infect Dis 1999; 28: 192–4
Denny FW, Loda FA. Acute respiratory infections are the leading cause of death in children in developing countries. Am J Trop Med Hyg 1986; 35: 1–2
World Health Organization. Pneumococcal vaccines: WHO position paper. Wkly Epidemiol Rec 1999; 74: 177–84
Henrichsen J. Typing of Streptococcus pneumoniae: past, present, and future. Am J Med 1999; 107: 50S–4S
Aniansson G, Alm B, Andersson B, et al. Nasopharyngeal colonization during the first year of life. J Infect Dis 1992; 165 Suppl. 1: S38–42
De Lencastre H, Kristinsson KG, Brito-Avo A, et al. Carriage of respiratory tract pathogens and molecular epidemiology of Streptococcus pneumoniae colonization in healthy children attending day care centers in Lisbon, Portugal. Microb Drug Resist 1999; 5: 19–29
Huebner RE, Wasas A, Mushi A, et al. Nasopharyngeal carriage and antimicrobial resistance in isolates of Streptococcus pneumoniae and Haemophilus influenzae type b in children under 5 years of age in Botswana. Int J Infect Dis 1998; 3: 18–25
Boken DJ, Chartrand SA, Moland ES, et al. Colonization with penicillin-nonsusceptible Streptococcus pneumoniae in urban and rural child-care centers. Pediatr Infect Dis J 1996; 15: 667–72
Bogaert D, Engelen MN, Timmers-Reker AJ,etal. Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study. J Clin Microbiol 2001; 39: 3316–20
Masuda K, Masuda R, Nishi J, et al. Incidences of nasopharyngeal colonization of respiratory bacterial pathogens in Japanese children attending day-care centers. Pediatr Int 2002; 44: 376–80
Syrogiannopoulos GA, Katopodis GD, Grivea IN, et al. Antimicrobial use and serotype distribution of nasopharyngeal Streptococcus pneumoniae isolates recovered from Greek children younger than 2 years old. Clin Infect Dis 2002; 35: 1174–82
Nilsson P, Laurell MH. Carriage of penicillin-resistant Streptococcus pneumoniae by children in day-care centers during an intervention program in Malmo, Sweden. Pediatr Infect Dis J 2001; 20: 1144–9
Kellner JD, Ford-Jones EL. Streptococcus pneumoniae carriage in children attending 59 Canadian child care centers: Toronto Child Care Centre Study Group. Arch Pediatr Adolesc Med 1999; 153: 495–502
Hjaltested EK, Bernatoniene J, Erlendsdottir H, et al. Resistance in respiratory tract pathogens and antimicrobial use in Icelandic and Lithuanian children. Scand J Infect Dis 2003; 35: 21–6
Lloyd-Evans N, O’Dempsey TJ, Baldeh I, et al. Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr Infect Dis J 1996; 15: 866–71
Adegbola RA, Falade AG, Sam BE, et al. The etiology of pneumonia in malnourished and well-nourished Gambian children. Pediatr Infect Dis J 1994; 13: 975–82
Mastro TD, Nomani NK, Ishaq Z, et al. Use of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in Pakistan for surveillance for antimicrobial resistance. Pediatr Infect Dis J 1993; 12: 824–30
Lankinen KS, Leinonen M, Tupasi TE, et al. Pneumococci in nasopharyngeal samples from Filipino children with acute respiratory infections. J Clin Microbiol 1994; 32: 2948–52
Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance — a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999; 18: 1–9
Jacobs MR, Dagan R, Appelbaum PC, et al. Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media. Antimicrob Agents Chemother 1998; 42: 589–95
Harrison CJ, Marks MI, Welch DF. Microbiology of recently treated acute otitis media compared with previously untreated acute otitis media. Pediatr Infect Dis 1985; 4: 641–6
Bluestone CD, Stephenson JS, Martin LM. Ten-year review of otitis media pathogens. Pediatr Infect Dis J 1992; 11: S7–11
Virolainen A, Salo P, Jero J, et al. Comparison of PCR assay with bacterial culture for detecting Streptococcus pneumoniae in middle ear fluid of children with acute otitis media. J Clin Microbiol 1994; 32: 2667–70
Eskola J, Kilpi T. Potential of bacterial vaccines in the prevention of acute otitis media. Pediatr Infect Dis J 2000; 19: S72–8
Pessey JJ, Gehanno P, Thoroddsen E, et al. Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate. Pediatr Infect Dis J 1999; 18: 854–9
Miller E, Waight P, Efstratiou A, et al. Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996–98. Acta Paediatr 2000; 89: 11–6
Sleeman K, Knox K, George R, et al. Invasive pneumococcal disease in England and Wales: vaccination implications. J Infect Dis 2001; 183: 239–46
Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era. JAMA 2001; 285: 1729–35
Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995: Active Surveillance Team. N Engl J Med 1997; 337: 970–6
Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 2002; 360: 211–8
Berg S, Trollfors B, Claesson BA, et al. Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden. Scand J Infect Dis 1996; 28: 247–52
Dagan R, Isaachson M, Lang R, et al. Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group. J Infect Dis 1994; 169: 912–6
Baraff LJ, Lee SI, Schriger DL. Outcomes of bacterial meningitis in children: a meta-analysis. Pediatr Infect Dis J 1993; 12: 389–94
Arditi M, Mason Jr EO, Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998; 102: 1087–97
Kornelisse RF, Westerbeek CM, Spoor AB, et al. Pneumococcal meningitis in children: prognostic indicators and outcome. Clin Infect Dis 1995; 21: 1390–7
Djuretic T, Ryan MJ, Miller E, et al. Hospital admissions in children due to pneumococcal pneumonia in England. J Infect 1998; 37: 54–8
McIntyre P, Gilmour R, Watson M. Differences in the epidemiology of invasive pneumococcal disease, metropolitan NSW, 1997–2001. N S W Public Health Bull 2003; 14: 85–9
Eskola J, Takala AK, Kela E, et al. Epidemiology of invasive pneumococcal infections in children in Finland. JAMA 1992; 268: 3323–7
Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993; 137: 977–88
Heiskanen-Kosma T, Korppi M, Jokinen C, et al. Etiology of childhood pneumonia: serologic results of a prospective, population-based study. Pediatr Infect Dis J 1998; 17: 986–91
von Kries R, Hermann M, Hachmeister A, et al. Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children. Pediatr Infect Dis J 2002; 21: 1017–23
Ziebold C, von Kries R, Siedler A, et al. Epidemiology of pneumococcal disease in children in Germany. Acta Paediatr Suppl 2000; 89: 17–21
Kaltoft MS, Zeuthen N, Konradsen HB. Epidemiology of invasive pneumococcal infections in children aged 0–6 years in Denmark: a 19-year nationwide surveillance study. Acta Paediatr Suppl 2000; 89: 3–10
Venetz I, Schopfer K, Muhlemann K. Paediatric, invasive pneumococcal disease in Switzerland, 1985–1994. Int J Epidemiol 1998; 27: 1101–4
Spanjaard L, van der EA, Rumke H, et al. Epidemiology of meningitis and bacteraemia due to Streptococcus pneumoniae in The Netherlands. Acta Paediatr Suppl 2000; 89: 22–6
Syriopoulou V, Daikos GL, Soulis K, et al. Epidemiology of invasive childhood pneumococcal infections in Greece. Acta Paediatr Suppl 2000; 89: 30–4
Usen S, Adegbola R, Mulholland K, et al. Epidemiology of invasive pneumococcal in the Western region, The Gambia. Paediatr Infect Dis J 1998; 17(1): 23–8
Obaro SK, Adegbola RA, Banya WA, et al. Carriage of pneumococci after pneumococcal vaccination. Lancet 1996; 348: 271–2
Dagan R, Melamed R, Muallem M, et al. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J Infect Dis 1996; 174: 1271–8
Dagan R, Muallem M, Melamed R, et al. Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid. Pediatr Infect Dis J 1997; 16: 1060–4
Mbelle N, Huebner RE, Wasas AD, et al. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis 1999; 180: 1171–6
Dagan R, Givon-Lavi N, Zamir O, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis 2002; 185: 927–36
Eskola J, Kilpi T, Palmu A, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001; 344: 403–9
Black S, Shinefield H, Fireman B, 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: 187–95
Kilpi T, Palmu A, Leinonen M, et al. Efficacy of a seven-valent pneumococcal conjugate vaccine (PncOMPC) against serotype-specific acute otitis media (AOM) caused by Streptococcus pneumoniae [abstract no. 689]. 40th Interscience Conference of Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto
Kilpi T, Palmu A, Leinonen M, et al. Effect of a seven-valent pneumococcal conjugate vaccine (PncOMPC) on acute otitis media (AOM) due to vaccine serotypes after boosting with conjugate or polysaccharide vaccine [abstract no. 24]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2001 Sep and Dec; Chicago (IL). Washington, DC: American Society for Microbiology, 2001: 35
Veenhoven RH, Bogaert D, Uiterwaal CSPM. Effect of pneumococcal vaccination on acute otitis media and nasopharyngeal carriage in children with recurrent otitis media [abstract no. 30]. 21st Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID); 2003 Apr 9–11; Sicily
Veenhoven R, Bogaert D, Uiterwaal C, et al. Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. Lancet 2003; 361: 2189–95
Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003; 348: 1737–46
Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997; 46: 1–24
Plouffe JF, Breiman RF, Facklam RR. Bacteremia with Streptococcus pneumoniae: implications for therapy and prevention. Franklin County Pneumonia Study Group. JAMA 1996; 275: 194–8
Rudolph KM, Parkinson AJ, Reasonover AL, et al. Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska, 1991–1998. J Infect Dis 2000; 182: 490–6
Laurichesse H, Grimaud O, Waight P, et al. Pneumococcal bacteraemia and meningitis in England and Wales, 1993 to 1995. Commun Dis Public Health 1998; 1: 22–7
McKenzie H, Reid N, Dijkhuizen RS. Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteraemia. J Med Microbiol 2000; 49: 361–6
Sankilampi U, Herva E, Haikala R, et al. Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland. Epidemiol Infect 1997; 118: 7–15
Huebner RE, Wasas AD, Klugman KP. Trends in antimicrobial resistance and serotype distribution of blood and cerebrospinal fluid isolates of Streptococcus pneumoniae in South Africa, 1991–1998. Int J Infect Dis 2000; 4: 214–8
Sarnaik S, Kaplan J, Schiffman G, et al. Studies on Pneumococcus vaccine alone or mixed with DTP and on Pneumococcus type 6B and Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in two- to five-year-old children with sickle cell anemia. published erratum appears in Pediatr Infect Dis J 1990 May; 9 (5): 308]. Pediatr Infect Dis J 1990; 9: 181–6
Vidarsson G, Sigurdardottir ST, Gudnason T, et al. Isotypes and opsonophagocytosis of pneumococcus type 6B antibodies elicited in infants and adults by an experimental pneumococcus type 6B-tetanus toxoid vaccine. Infect Immun 1998; 66: 2866–70
Sigurdardottir ST, Vidarsson G, Gudnason T, et al. Immune responses of infants vaccinated with serotype 6B pneumococcal polysaccharide conjugated with tetanus toxoid. Pediatr Infect Dis 1997; 16: 667–74
Steinhoff MC, Edwards K, Keyserling H, et al. A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children: effect of polysaccharide size and linkage characteristics. Pediatr Infect Dis 1994; 13: 368–72
O’Brien KL, Steinhoff MC, Edwards K, et al. Immunologic priming of young children by pneumococcal glycoprotein conjugate, but not polysaccharide, vaccines. Pediatr Infect Dis 1996; 15: 425–30
Käyhty H, Ahman H, Ronnberg PR, et al. Pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine is immunogenic in infants and children. J Infect Dis 1995; 172: 1273–8
Arguedas A, Loaiza C, Perez A. A randomized, placebo-controlled, dose-range study to evaluate the immunogenicity of a tetravalent pneumococcal protein D conjugate vaccine in infants, and boostability by plain polysaccharide [abstract]. The 19th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID); 2001 Mar 26–28; Istanbul, 21
Nieminen T, Käyhty H, Leroy O, et al. Pneumococcal conjugate vaccination in toddlers: mucosal antibody response measured as circulating antibody-secreting cells and as salivary antibodies. Pediatr Infect Dis J 1999; 18: 764–72
Dagan R, Melamed R, Zamir O, et al. Safety and immunogenicity of tetravalent pneumococcal vaccines containing 6B, 14, 19F and 23F polysaccharides conjugated to either tetanus toxoid or diphtheria toxoid in young infants and their booster-ability by native polysaccharide antigens. Pediatr Infect Dis 1997; 16: 1053–9
Ahman H, Käyhty H, Lehtonen H, et al. Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce immunological memory. Pediatr Infect Dis J 1998; 17: 211–6
Ahman H, Käyhty H, Vuorela A, et al. Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid. Vaccine 1999; 17: 2726–32
King Jr JC, Vink PE, Farley JJ, et al. Comparison of the safety and immunogenicity of a pneumococcal conjugate with a licensed polysaccharide vaccine in human immunodeficiency virus and non-human immunodeficiency virus-infected children. Pediatr Infect Dis J 1996; 15: 192–6
Pichichero ME, Shelly MA, Treanor JJ. Evaluation of a pentavalent conjugated pneumococcal vaccine in toddlers. Pediatr Infect Dis 1997; 16: 72–4
Leach A, Ceesay SJ, Banya WA, et al. Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate vaccine in Gambian infants. Pediatr Infect Dis 1996; 15: 333–9
Ahman H, Käyhty H, Tamminen P, et al. Pentavalent pneumococcal oligosaccharide conjugate vaccine PncCRM is well-tolerated and able to induce an antibody response in infants. Pediatr Infect Dis 1996; 15: 134–9
Daum RS, Hogerman D, Rennels MB, et al. Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines. J Infect Dis 1997; 176: 445–55
Obaro SK, Huo Z, Banya WAS, et al. A glycoprotein pneumococcal conjugate vaccine primes for antibody responses to a pneumococcal polysaccharide vaccine in Gambian children. Pediatr Infect Dis J 1997; 16: 1135–40
King Jr JC, Vink PE, Farley JJ, et al. Safety and immunogenicity of three doses of a five-valent pneumococcal conjugate vaccine in children younger than two years with and without human immunodeficiency virus infection. Pediatrics 1997; 99: 575–80
Blum MD, Dagan R, Mendelman PM, et al. A comparison of multiple regimens of pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers. Vaccine 2000; 18: 2359–67
Anderson EL, Kennedy DJ, Geldmacher KM, et al. Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants. J Pediatr 1996; 128: 649–53
Miernyk KM, Parkinson AJ, Rudolph KM, et al. Immunogenicity of a heptavalent pneumococcal conjugate vaccine in Apache and Navajo Indian, Alaska native and non-native American children. Clin Infect Dis 2000; 31: 34–41
Vernacchio L, Neufeld EJ, MacDonald K, et al. Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease. J Pediatr 1998; 133: 275–8
Sorensen RU, Leiva LE, Giangrosso PA, et al. Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine. Pediatr Infect Dis J 1998; 17: 685–91
Zielen S, Buhring I, Strnad N, et al. Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine. Infect Immun 2000; 68: 1435–40
Barnett ED, Pelton SI, Cabral HJ, et al. Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children. Clin Infect Dis 1999; 29: 191–2
O’Brien KL, Swift AJ, Winkelstein JA, et al. Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM(197) among infants with sickle cell disease. Pediatrics 2000; 106: 965–72
Rennels MB, Edwards KM, Keyserling HL, et al. Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 in United States infants. Pediatrics 1998; 101: 604–11
Shinefield HR, Black S, Ray P, et al. Safety and immunogenicity of heptavalent pneumococcal CRM 197 conjugate vaccine in infants and toddlers. Pediatr Infect Dis J 1999; 18: 757–63
Choo S, Seymour L, Morris R, et al. Immunogenicity and reactogenicity of a pneumococcal conjugate vaccine administered combined with a Haemophilus influenzae type b conjugate vaccine in United Kingdom infants. Pediatr Infect Dis J 2000; 19: 854–62
Nurkka A, Ahman H, Korkeila M, et al. Serum and salivary anti-capsular antibodies in infants and children immunized with the heptavalent pneumococcal conjugate vaccine PncCRM. Pediatr Infect Dis J 2001; 20: 25–33
O’Brien KL, Moulton LH, Reid R, et al. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial. Lancet 2003; 362: 355–61
Jonsdottir I, Sigurdardottir S, Gudnason I. Concomitant administration of octavalent pneumococcal polysaccharide conjugate vaccine, Pnm-D, and Haemophilus influenzae conjugate vaccine, PRP-D, sharing the carrier DT, may induce interference in infants [abstract]. The 2nd International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD); 2003 Mar 19–23; Sun City, 39
Nurkka A, Ahman H, Yaich M, et al. Serum and salivary anticapsular antibodies in infants and children vaccinated with octavalent pneumococcal conjugate vaccines, PncD and PncT. Vaccine 2001; 20: 194–201
Goldblatt D, Akoto O, Ashton L, et al. Does one dose of pneumococcal conjugate vaccine induce immunological memory in toddlers [abstract]. 40th Interscience Conference of Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 17
Obaro SK, Adegbola RA, Chang I, et al. Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants. Pediatr Infect Dis J 2000; 19: 463–9
Gatchalian S, Borja-Tabora C, Bermel N, et al. A randomized, placebo-controlled study to evaluate the immunogenicity of an 11-valent pneumococcal protein D conjugate vaccine administered as primary vaccination to infants at 6, 10 and 14 weeks of age [abstract]. The 19th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID); 2001 Mar 26–28; Istanbul, 18
Puumalainen T, Zeta-Capeding MR, Käyhty H, et al. Antibody response to an eleven valent diphtheria- and tetanus-conjugated pneumococcal conjugate vaccine in Filipino infants. Pediatr Infect Dis J 2002; 21: 309–14
Puumalainen T, Dagan R, Wuorimaa T, et al. Greater antibody responses to an eleven valent mixed carrier diphtheria- or tetanus-conjugated pneumococcal vaccine in Filipino than in Finnish or Israeli infants. Pediatr Infect Dis J 2003; 22: 141–9
Sigurdardottir S, Gudnason T, Kristinsson KG, et al. Safety and immunogenicity of two different formulations of 11-valent pneumococcal polysaccharide conjugate vaccines, F3 and F3bis in healthy Icelandic infants [abstract no. P50]. Presented at the Second International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD); 2000 Mar 19–23; Sun City, 50
Wuorimaa T, Dagan R, Eskola J, et al. Tolerability and immunogenicity of an eleven-valent pneumococcal conjugate vaccine in healthy toddlers. Pediatr Infect Dis J 2001; 20: 272–7
Jonsdottir I, Ingolfsdottir G, Saeland E, et al. A single dose of pneumococcal conjugate vaccine elicits functional antibodies and induces memory in toddlers [poster]. 40th Interscience Conference of Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 235
Coffey TJ, Enright MC, Daniels M, et al. Recombinational exchanges at the capsular polysaccharide biosynthetic locus lead to frequent serotype changes among natural isolates of Streptococcus pneumoniae. Mol Microbiol 1998; 27: 73–83
Reinert RR, Kaufhold A, Schlaeger JJ, et al. Serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates causing systemic infections among children in Germany, 1992 to 1996. Pediatr Infect Dis J 1997; 16: 244–5
Fenoll A, Jado I, Vicioso D, et al. Evolution of Streptococcus pneumoniae serotypes and antibiotic resistance in Spain: update (1990 to 1996). J Clin Microbiol 1998; 36: 3447–54
Hedlund J, Svenson SB, Kalin M, et al. Incidence, capsular types, and antibiotic susceptibility of invasive Streptococcus pneumoniae in Sweden. Clin Infect Dis 1995; 21: 948–53
Magnus T, Andersen BM. Serotypes and resistance patterns of Streptococcus pneumoniae causing systemic disease in northern Norway. Eur J Clin Microbiol Infect Dis 1995; 14: 229–34
Kyaw MH, Clarke S, Edwards GF, et al. Serotypes/groups distribution and antimicrobial resistance of invasive pneumococcal isolates: implications for vaccine strategies. Epidemiol Infect 2000; 125: 561–72
Hausdorff WP. Invasive pneumococcal disease in children: geographic and temporal variations in incidence and serotype distribution. Eur J Pediatr 2002; 161 Suppl. 2: S135–9
Fraser D, Givon-Lavi N, Bilenko N, et al. A decade (1989–1998) of pediatric invasive pneumococcal disease in 2 populations residing in 1 geographic location: implications for vaccine choice. Clin Infect Dis 2001; 33: 421–7
Koskela M, Leinonen M, Haiva VM, et al. First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants. Pediatr Infect Dis 1986; 5: 45–50
Temple K, Greenwood B, Inskip H, et al. Antibody response to pneumococcal capsular polysaccharide vaccine in African children. Pediatr Infect Dis J 1991; 10: 386–90
Douglas RM, Paton JC, Duncan SJ, et al. Antibody response to pneumococcal vaccination in children younger than five years of age. J Infect Dis 1983; 148: 131–7
Leinonen M, Sakkinen A, Kalliokoski R, et al. Antibody response to 14-valent pneumococcal capsular polysaccharide vaccine in pre-school age children. Pediatr Infect Dis 1986; 5: 39–44
Lim PL, Lau YL. Occurrence of IgG subclass antibodies to ovalbumin, avidin, and pneumococcal polysaccharide in children. Int Arch Allergy Immunol 1994; 104: 137–43
Sell SH, Wright PF, Vaughn WK, et al. Clinical studies of pneumococcal vaccines in infants. I: reactogenicity and immunogenicity of two polyvalent polysaccharide vaccines. Rev Infect Dis 1981; 3 Suppl.: S97–107
Borgono JM, McLean AA, Vella PP, et al. Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants. Proc Soc Exp Biol Med 1978; 157: 148–54
Karma P, Pukander J, Sipila M, et al. Prevention of otitis media in children by pneumococcal vaccination. Am J Otolaryngol 1985; 6: 173–84
Makela PH, Sibakov M, Herva E, et al. Pneumococcal vaccine and otitis media. Lancet 1980; II: 547–51
Lee HJ, Kang JH, Henrichsen J, et al. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in healthy children and in children at increased risk of pneumococcal infection. Vaccine 1995; 13: 1533–8
Witt CS, Pomat W, Lehmann D, et al. Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea. Clin Exp Immunol 1991; 83: 219–24
Paton JC, Toogood IR, Cockington RA, et al. Antibody response to pneumococcal vaccine in children aged 5 to 15 years. Am J Dis Child 1986; 140: 135–8
Bjornson AB, Falletta JM, Verter JI, et al. Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis. J Pediatr 1996; 129: 828–35
Fuchshuber A, Kuhnemund O, Keuth B, et al. Pneumococcal vaccine in children and young adults with chronic renal disease. Nephrol Dial Transplant 1996; 11: 468–73
Spika JS, Halsey NA, Le CT, et al. Decline of vaccine-induced antipneumococcal antibody in children with nephrotic syndrome. Am J Kidney Dis 1986; 7: 466–70
Rao SP, Rajkumar K, Schiffman G, et al. Anti-pneumococcal antibody levels three to seven years after first booster immunization in children with sickle cell disease, and after a second booster. J Pediatr 1995; 127: 590–2
Vernacchio L, Romero-Steiner S, Martinez JE, et al. Comparison of an opsonophagocytic assay and IgG ELISA to assess responses to pneumococcal polysaccharide and pneumococcal conjugate vaccines in children and young adults with sickle cell disease. J Infect Dis 2000; 181: 1162–6
Granoff DM, Gupta RK, Belshe RB, et al. Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination. J Infect Dis 1998; 178: 870–4
Zhang Q, Choo S, Everard J, et al. Mucosal immune responses to meningococcal group C conjugate and group A and C polysaccharide vaccines in adolescents. Infect Immun 2000; 68: 2692–7
Artenstein MS, Brandt BL. Immunologic hyporesponsiveness in man to group C meningococcal polysaccharide. J Immunol 1975; 115: 5–7
Torling J, Hedlund J, Konradsen HB, et al. Revaccination of elderly persons with the 23-valent pneumococcal polysaccharide vaccine [abstract]. 3rd International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD); 2002 May 5–9; Anchorage
French N, Nakiyingi J, Carpenter LM, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet 2000; 355: 2106–11
Spoulou V, Theodoridou M, Papaevangelou VG, et al. 23-Valent pneumococcal vaccination and HIV. Lancet 2000; 356: 1027–8
Stein KE. Thymus-independent and thymus-dependent responses to polysaccharide antigens. J Infect Dis 1992; 165 Suppl. 1: S49–52
Siber GR. Pneumococcal disease: prospects for a new generation of vaccines. Science 1994; 265: 1385–7
Wuorimaa T, Dagan R, Vakevainen M, et al. Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant. J Infect Dis 2001; 184: 1211–5
Goldblatt D, Vaz AR, Miller E. Antibody avidity as a surrogate marker of successful priming by Haemophilus influenzae type b conjugate vaccines following infant immunization. J Infect Dis 1998; 177: 1112–5
Eskola J. Immunogenicity of pneumococcal conjugate vaccines. Pediatr Infect Dis J 2000; 19: 388–93
Anttila M, Eskola J, Ahman H, et al. Avidity of IgG for Streptococcus pneumoniae type 6B and 23F polysaccharides in infants primed with pneumococcal conjugates and boosted with polysaccharide or conjugate vaccines. J Infect Dis 1998; 177: 1614–21
Anttila M, Voutilainen M, Jantti V, et al. Contribution of serotype-specific IgG concentration, IgG subclasses and relative antibody avidity to opsonophagocytic activity against Streptococcus pneumoniae. Clin Exp Immunol 1999; 118: 402–7
Anttila M, Eskola J, Ahman H, et al. Differences in the avidity of antibodies evoked by four different pneumococcal conjugate vaccines in early childhood. Vaccine 1999; 17: 1970–7
Soininen A, Seppala I, Nieminen T, et al. IgG subclass distribution of antibodies after vaccination of adults with pneumococcal conjugate vaccines. Vaccine 1999; 17: 1889–97
Lottenbach KR, Mink CM, Barenkamp SJ, et al. Age-associated differences in immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to pneumococcal polysaccharides following vaccination. Infect Immun 1999; 67: 4935–8
Käyhty H, Ahman H, Eriksson K, et al. Pneumococcal conjugate vaccine (PNMCRM) is immunogenic when administered at 3, 5 and 12 months of age [abstract no. 263]. 21st Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID); 2003 Apr 9–11; Sicily
Obaro SK. Protein conjugate vaccines: how much is enough? Trends Microbiol 2001; 9: 364–5
Gold R, Lepow ML, Goldschneider I, et al. Kinetics of antibody production to group A and group C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children. J Infect Dis 1979; 140: 690–7
Gold R, Lepow ML, Goldschneider I, et al. Antibody responses of human infants to three doses of group A Neisseria meningitidis polysaccharide vaccine administered at two, four, and six months of age. J Infect Dis 1978; 138: 731–5
Gold R, Lepow ML, Goldschneider I, et al. Immune response of human infants of polysaccharide vaccines of group A and C Neisseria meningitidis. J Infect Dis 1977; 136 Suppl.: S31–5
Anttila M, Eskola J, Käyhty H. Opsonic activity and concentration of antibody to Streptococcus pneumoniae type 6B [abstract no. 599]. 35th Annual Meeting of the Infectious Diseases Society of America; 1997 Sep 13–16; San Francisco
Nieminen T, Eskola J, Käyhty H. Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell response and humoral antibody responses in saliva and in serum. Vaccine 1998; 16: 630–6
Dagan R, Eskola J, Leclerc C, et al. Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants. Infect Immun 1998; 66: 2093–8
Wuorimaa T, Käyhty H, Leroy O, et al. Tolerability and immunogenicity of an 11-valent pneumococcal conjugate vaccine in adults. Vaccine 2001; 19: 1863–9
Takala AK, Eskola J, Leinonen M, et al. Reduction of oropharyngeal carriage of Haemophilus influenzae type b (Hib) in children immunized with an Hib conjugate vaccine. J Infect Dis 1991; 164: 982–6
Kauppi M, Eskola J, Käyhty H. Anti-capsular polysaccharide antibody concentrations in saliva after immunization with Haemophilus influenzaetype b conjugate vaccines. Pediatr Infect Dis J 1995; 14: 286–94
Barbour ML, Mayon-White RT, Coles C, et al. The impact of conjugate vaccine on carriage of Haemophilus influenzae type b. J Infect Dis 1995; 171: 93–8
Choo S, Zhang Q, Seymour L, et al. Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants. J Infect Dis 2000; 182: 1260–3
Korkeila M, Lehtonen H, Ahman H, et al. Salivary anticapsular antibodies in infants and children immunised with Streptococcuspneumoniae capsular polysaccharides conjugated to diphtheria or tetanus toxoid. Vaccine 2000; 18: 1218–26
Lakshman R, Murdoch C, Race G, et al. Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy. Arch Dis Child 2003; 88: 211–4
Soininen A, Pursiainen H, Kilpi T, et al. Natural development of antibodies to pneumococcal capsular polysaccharides depends on the serotype: association with pneumococcal carriage and acute otitis media in young children. J Infect Dis 2001; 184: 569–76
Darville T, Jacobs RF, Lucas RA, et al. Detection of Haemophilus influenzae type b antigen in cerebrospinal fluid after immunisation. Pediatr Infect Dis J 1992; 11: 243–4
Spinola ST, Sheaffer CI, Philbrick KB, et al. Antigenuria after Haemophilus influenzae type b polysaccharide immunisation: a prospective study. J Pediatr 1986; 108: 247–9
Brokstad KA, Cox RJ, Olofsson J, et al. Parenteral influenza vaccination induces a rapid systemic and local immune response. J Infect Dis 1995; 171: 198–203
Coffin SE, Clark SL, Bos NA, et al. Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization. J Immunol 1999; 163: 3064–70
Janoff EN, Fasching C, Orenstein JM, et al. Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes. J Clin Invest 1999; 104: 1139–47
Johnson S, Opstad NL, Douglas JM, et al. Prolonged and preferential production of polymeric immunoglobulin A in response to Streptococcus pneumoniae capsular polysaccharides. Infect Immun 1996; 64: 4339–44
Rapola S, Jantti V, Haikala R, 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: 1146–52
Virolainen A, Russell W, Crain MJ, et al. Human antibodies to pneumococcal surface protein A in health and disease. Pediatr Infect Dis J 2000; 19: 134–8
Zhang Q, Choo S, Finn A. Immune responses to novel pneumococcal proteins (Pneumolysin, PspA, PsaA and CbpA) in adenoidal B cells from children. Infect Immun 2002; 70: 5363–9
Douglas RM, Miles HB. Vaccination against Streptococcus pneumoniae in childhood: lack of demonstrable benefit in young Australian children. J Infect Dis 1984; 149: 861–9
Rosen C, Christensen P, Hovelius B, et al. Effect of pneumococcal vaccination on upper respiratory tract infections in children: design of a follow-up study. Scand J Infect Dis Suppl 1983; 39: 39–44
Makela PH, Leinonen M, Pukander J, et al. A study of the pneumococcal vaccine in prevention of clinically acute atttacks of recurrent otitis media. Rev Infect Dis 1981; 3 Suppl.: S124–32
Makela PH, Karma P, Sipila M, et al. Possibilities of preventing otitis media by vaccination. Scand J Infect Dis Suppl 1983; 39: 34–8
Teele DW, Klein JO, Bratton L, et al. Use of pneumococcal vaccine for prevention of recurrent acute otitis media in infants in Boston: the Greater Boston Collaborative Otitis Media Study Group. Rev Infect Dis 1981; 3 Suppl.: S113–8
Howie VM, Ploussard J, Sloyer JL, et al. Use of pneumococcal polysaccharide vaccine in preventing otitis media in infants: different results between racial groups. Pediatrics 1984; 73: 79–81
Riley ID, Lehmann D, Alpers MP. Pneumococcal vaccine trials in Papua New Guinea: relationships between epidemiology of pneumococcal infection and efficacy of vaccine. Rev Infect Dis 1991; 13 Suppl. 6: S535–41
Riley ID, Lehmann D, Alpers MP, et al. Pneumococcal vaccine prevents death from acute lower-respiratory-tract infections in Papua New Guinean children. Lancet 1986; II: 877–81
Lehmann D, Marshall TF, Riley ID,et al. Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children. Ann Trop Paediatr 1991; 11: 247–57
Fiore AE, Levine OS, Elliott JA, et al. Effectiveness of pneumococcal polysaccharide vaccine for preschool-age children with chronic disease. Emerg Infect Dis 1999; 5: 828–31
MacDonald NE, Halperin SA, Law BJ, et al. Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial. JAMA 1998; 280: 1685–9
Shinefield H, Black S, Ray P, et al. Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants. Pediatr Infect Dis J 2002; 21: 182–6
O’Brien KL, Moulton L, Reid R, et al. Invasive disease efficacy of a 7-valent pneumococcal conjugate vaccine among Navajo and White Mountain Apache (N/WMA) children [abstract no. 1371]. Pediatric Academic Society Annual Meeting; 2001 Apr 28–May 1; Baltimore
O’Brien KL, Moulton L, Reid R, et al. Invasive disease efficacy of a 7-valent pneumococcal conjugate vaccine among Navajo and White Mountain Apache (N/WMA) children [abstract]. 19th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID); 2001 Mar 26–28; Istanbul, 4
Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003; 349: 1341–8
Sigurdardottir ST, Ingolfsdottir G, Davidsdottir K, et al. Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine. Pediatr Infect Dis J 2002; 21: 548–54
Dagan R, Givon S, Yagupsky P, et al. Effect of a 9-valent pneumococcal CRM vaccine (PnmCRM9) on nasopharyngeal carriage of vaccine type and non-vaccine type S. pneumoniae strains among day care center attendees. In: Program and Abstracts of the 38th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Soceity for Microbiology, 1998: 299
Dagan R, Zamir O, Tirosh N, et al. Nasopharyngeal (NP) carriage of Streptococcus pneumoniae (pnc) in toddlers vaccinated during infancy with an 11-valent pneumococcal vaccine conjugated to diphteria and tetanus toxoids (PCV-DT) [abstract no. 47]. 40th Interscience Conference of Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 236
Sigurdardottir ST, Kristinsson KG, Ingolfsdottir GI, et al. Nasopharyngeal (NP) carriage of vacine serotype pneumococci is more common in children who respond poorly to the 11-valent pneumococcal conjugate [abstract]. The 3rd International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD); 2002 May 5–8; Anchorage, 4029
Kilpi TM, Syrjanen R, Palmu A, et al. Parallel evaluation of the effect of a 7-valent pneumococcal conjugate vaccine (PNC-CRM) on pneumococcal carriage and acute otitis media [abstract]. 19th Annual Meeting of the European Society for Paediatric Infectious Diseass (ESPID); 2001 Mar 26–28; Istanbul, 4
Edwards KM, Wandling G, Palmer P, et al. Carriage of pneumococci among infants immunized with a 9-valent pneumococcal (Pnc) conjugate vaccine at 2, 4 and 6 months of age [abstract no. 34]. Clin Infect Dis 1999; 29: 966
Millar EV, O’Brien KL, Watt JP, et al. Duration of protection against pneumococca; nasopharyngeal carriage by 7-valent pneumococcal conjugate vaccine (PnCRM7) in Navajo and Apache children [poster]. 3rd International Symposium on Pneumococci and Pneumococcal Diseases (ISPDD); 2002 May 5–8; Anchorage
Nohnynek HM, Lucero MG, Ollgren J, et al. Effect of 11-valent pneumococcal (Pnm) conjugate vaccine (11PnmTD) on nasopharyngeal carriage of Pnm in Filipino children [abstract]. 3rd International Symposium on Pneumococci and Pneumococcal Disease; 2002 5–8 May; Anchorage, 53–4
Ghaffar FA, Barton T, Muniz LS, et al. Effect of the 7-valent pneumococcal conjugate vaccine (PCV-7) on nasopharyngeal colonization by Streptococcus pneumoniae early in life [abstract no. G-834]. In: Proceedings of the 42nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego. Washington, DC: American Society of Microbiology, 2002: 242
Kilpi T, Ahman H, Jokinen 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: 1155–64
Dagan R, Sikuler-Cohen M, Zamir O, et al. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees. Pediatr Infect Dis J 2001; 20: 951–8
Black SB, Shinefield HR, Ling S, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J 2002; 21: 810–5
Dagan R, Melamed R, Muallem M, et al. Nasopharyngeal colonization in southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: relation to serotypes likely to be included in pneumococcal conjugate vaccines. J Infect Dis 1996; 174: 1352–5
Dagan R, Givon-Lavi N, Fraser D. Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J 2003; 22: 532–40
Black SB, Shinefield H, Hansen J, et al. Postlicensure evaluation of the effectiveness of seven valent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2001; 20: 1105–7
Black SM. Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser permanente. Pediatr Infect Dis J 2004; 23: 485–9
Hammitt LL, Bruden D, Butler JC, et al. Indirect effect of childhood heptavalent pneumococcal conjugate vaccination on adult carriage of Streptococcus pneumoniae: a community study [abstract]. 4th International Symposium on Pneumococci and Pneumococcal Diseases; 2004 May 9–13; Helsinki, 35
Black S, Shinefield H. Safety and efficacy of the seven-valent pneumococcal conjugate vaccine: evidence from Northern California. Eur J Pediatr 2002 Dec; 161 Suppl. 2: S127–31
Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000; 49: 1–35
American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics 2000; 106: 362–6
Choo S, Finn A. New pneumococcal vaccines for children. Arch Dis Child 2001; 84: 289–94
Donaldson L, Mullally S, Smith J. Extending meningitis C vaccine to 20–24 year olds; pneumococcal vaccine for at-risk under 2 year olds; CMO Newsletter 2002 Jan 4. London: HMSO.
Finn A, Booy R, Moxon R, et al. Should the new pneumococcal vaccine be used in high-risk children? Arch Dis Child 2002; 87: 18–21
Brooks-Walter A, Briles DE, Hollingshead SK. 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 1999; 67: 6533–42
Hammerschmidt S, Talay SR, Brandtzaeg P, et al. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol Microbiol 1997; 25: 1113–24
Janulczyk R, Iannelli F, Sjoholm AG, et al. Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function. J Biol Chem 2000; 275: 37257–63
Rosenow C, Ryan P, Weiser JN, et al. Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 1997; 25: 819–29
Briles DE, Tart RC, Swiatlo E, et al. Pneumococcal diversity: considerations for new vaccine strategies with emphasis on pneumococcal surface protein A (PspA). Clin Microbiol Rev 1998; 11: 645–57
Paton JC. Novel pneumococcal surface proteins: role in virulence and vaccine potential. Trends Microbiol 1998; 6: 85–7
Morrison KE, Lake D, Crook J, et al. Confirmation of psaA in all 90 serotypes of Streptococcus pneumoniae by PCR and potential of this assay for identification and diagnosis. J Clin Microbiol 2000; 38: 434–7
Alexander JE, Lock RA, Peeters CC, et al. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect Immun 1994; 62: 5683–8
Briles DE, Hollingshead S, Brooks-Walter A, et al. The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection. Vaccine 2000; 18: 1707–11
Briles DE, Ades E, Paton JC, et al. 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: 796–800
Simell B, Korkeila M, Pursiainen H, et al. Pneumococcal carriage and otitis media induce salivary antibodies to Pneumococcal Surface Adhesin A, Pneumolysin, and Pneumococcal Surface Protein A in children. J Infect Dis 2001; 183: 887–96
Berry AM, Paton JC. Sequence heterogeneity of PsaA, a 37-kilodalton putative adhesin essential for virulence of Streptococcus pneumoniae. Infect Immun 1996; 64: 5255–62
McDaniel LS, Sheffield JS, Delucchi P, et al. PspA, a surface protein of Streptococcus pneumoniae,is capable of eliciting protection against pneumococci of more than one capsular type. Infect Immun 1991; 59: 222–8
Madsen M, Lebenthal Y, Cheng Q, et al. A pneumococcal protein that elicits interleukin-8 from pulmonary epithelial cells. J Infect Dis 2000; 181: 1330–6
Kim JJ, Nottingham LK, Sin JI, et al. CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines. J Clin Invest 1998; 102: 1112–24
Nabors GS, Braun PA, Herrmann DJ, 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: 1743–54
Robbins JB, Pittman M, Trollfors B, et al. Primum non nocere: a pharmacologically inert pertussis toxoid alone should be the next pertussis vaccine. Pediatr Infect Dis J 1993; 12: 795–807
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Bernatoniene, J., Finn, A. Advances in Pneumococcal Vaccines. Drugs 65, 229–255 (2005). https://doi.org/10.2165/00003495-200565020-00005
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DOI: https://doi.org/10.2165/00003495-200565020-00005