Drugs & Aging

, Volume 24, Issue 10, pp 791–800 | Cite as

Advances in Pneumococcal Vaccines

What are the Advantages for the Elderly?
Current Opinion


Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. There are three established approaches to pneumococcal vaccination: polysaccharide vaccines, protein-polysaccharide conjugate vaccines and protein-based vaccines. This article reviews advances in anti-pneumococcal vaccines, with reference to advantages and shortcomings for the elderly in particular.

The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for high-risk patients and the general elderly population. Although the effectiveness of PPV against pneumonia is unclear, recent studies point to significant protective effects in preventing pneumococcal pneumonia and reducing the severity of disease in vaccinated elderly patients. PPV offers high serotype coverage and, although it is poorly immunogenic in some individuals, provides approximately 60% protection against invasive disease in the general elderly population. PPV vaccination appears cost effective for elderly patients although the vaccine might only be effective in preventing invasive disease. Additional benefits could mean a greater level of vaccine cost effectiveness. However, it is important to understand that PPV provides incomplete protection, especially in those with underlying high-risk conditions, and development of more effective pneumococcal vaccination strategies for elderly patients is still needed.

In recent years, the most important advance in the prevention of pneumococcal infections in the elderly has been the introduction of a 7-valent conjugate pneumococcal vaccine (CPV) as a routine vaccination for infants. In addition to dramatically reducing invasive infection in children, CPV has been observed to have a considerable indirect protective effect in parents and grandparents. While the possibility of using CPV in elderly patients has been suggested, currently there are only limited immunogenicity data and no efficacy data in adults. The low serotype coverage is an important shortcoming and if CPV were to be used in the elderly, it would need to be given sequentially with the PPV. New CPVs covering more serotypes are currently under investigation, and these could be an alternative for use in all groups in the future.

Numerous protein-based vaccine candidates offer the potential advantage of prevention against infections caused by all pneumococcal serotypes. Several are in various stages of development in animal models, but none can be expected to be available in clinical practice for several years at least.

To date, the 23-valent PPV is still the best anti-pneumococcal vaccine option in the management of elderly persons. Introduction of the 7-valent CPV as a routine vaccine for children has provided considerable indirect benefits for older adults via herd immunity, but this vaccine has limited serotype coverage in elderly individuals. New CPVs including more serotypes (various CPVs are in different phases of pre-licensure studies) could prove to be good options in the future for all age groups. Several protein-based pneumococcal vaccine candidates (currently under investigation in animal models) offer the potential advantage of serotype independent protection, but none can be expected to be available in clinical practice in the near future.


Conjugate Vaccine Invasive Pneumococcal Disease Pneumococcal Vaccine Pneumococcal Pneumonia Pneumococcal Infection 



No sources of funding were used to assist in the preparation of this article. The author has no conflicts of interest that are directly relevant to the content of this article.


  1. 1.
    Butler JC, Schuchat A. Epidemiology of pneumococcal infections in the elderly. Drugs Aging 1999; 15Suppl. 1: 11–9PubMedCrossRefGoogle Scholar
  2. 2.
    Ortqvist A, Hedlund J, Kalin M. Streptococcus pneumoniae: epidemiology, risk factors, and clinical features. Semin Respir Crit Care Med 2005; 26(6): 563–74PubMedCrossRefGoogle Scholar
  3. 3.
    Fedson DS. Pneumococcal vaccination for older adults: the first 20 years. Drugs Aging 1999; 15Suppl. 1: 21–30PubMedCrossRefGoogle Scholar
  4. 4.
    Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 2005; 5(2): 83–93PubMedGoogle Scholar
  5. 5.
    Rubins JB, Janoff EN. Pneumococcal disease in the elderly: what is preventing vaccine efficacy? Drugs Aging 2001; 18(5): 305–11PubMedCrossRefGoogle Scholar
  6. 6.
    Ortqvist A. Pneumococcal vaccination: current and future issues. Eur Respir J 2001; 18(1): 184–95PubMedCrossRefGoogle Scholar
  7. 7.
    Bogaert D, Hermans PW, Adrian PV, et al. Pneumococcal vaccines: an update on current strategies. Vaccine 2004; 22(17–18): 2209–20PubMedCrossRefGoogle Scholar
  8. 8.
    Fedson DS, Musher DM. Pneumococcal polysaccharide vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th ed. Philadelphia (PA): Saunders, 2003: 529–88Google Scholar
  9. 9.
    Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR Morb Mortal Wkly Rep 1997; 46(RR-8): 1–24Google Scholar
  10. 10.
    Sankilampi U, Honkanen PO, Bloigu A, et al. Antibody response to pneumococcal capsular polysaccharide vaccine in the elderly. J Infect Dis 1996; 173: 387–93PubMedCrossRefGoogle Scholar
  11. 11.
    Artz AS, Ershler WB, Longo DL. Pneumococcal vaccination and revaccination of older adults. Clin Microbiol Rev 2003; 16(2): 308–18PubMedCrossRefGoogle Scholar
  12. 12.
    Fine MJ, Smith MA, Carson CA, et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis of randomized controlled trials. Arch Intern Med 1994; 154: 2666–77PubMedCrossRefGoogle Scholar
  13. 13.
    Hutchison BG, Oxman AD, Shannon HS, et al. Clinical effectiveness of pneumococcal vaccine: meta-analysis. Can Fam Physician 1999; 45: 2381–93PubMedGoogle Scholar
  14. 14.
    Moore RA, Wiffen PJ, Lipsky BA. Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials. BMC Fam Pract 2000; 1: 1PubMedCrossRefGoogle Scholar
  15. 15.
    Cornu C, Yzebe D, Leophonte P, et al. Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis of randomized trials. Vaccine 2001; 19: 4780–90PubMedCrossRefGoogle Scholar
  16. 16.
    Puig-Barbera J, Belenguer Varea A, Goterris-Pinto M, et al. Pneumococcal vaccine effectiveness in the elderly: systematic review and meta-analysis [in Spanish]. Aten Primaria 2002; 30(5): 269–81PubMedGoogle Scholar
  17. 17.
    Mantagni P, Cutts F, Hall AJ. Efficacy of polysaccharide pneumococcal vaccine in adults in more developed countries: the state of the evidence. Lancet Infect Dis 2003; 3: 71–8CrossRefGoogle Scholar
  18. 18.
    Watson L, Wilson BJ, Waugh N. Pneumococcal polysaccharide vaccine: a systematic review of clinical effectiveness in adults. Vaccine 2002; 20: 2166–73PubMedCrossRefGoogle Scholar
  19. 19.
    Dear K, Holden J, Andrews R, et al. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2003; (4): CD000422Google Scholar
  20. 20.
    Fedson DS, Lise C. Precise answers to the wrong question: prospective clinical trials and the meta-analyses of pneumococcal vaccine in elderly and high-risk adults. Vaccine 2004; 22: 927–46PubMedCrossRefGoogle Scholar
  21. 21.
    Melegaro A, Edmunds WJ. The 23-valent pneumococcal polysaccharide vaccine: part I. Efficacy of PPV in the elderly: comparison of meta-analyses. Eur J Epidemiol 2004; 19: 353–63PubMedCrossRefGoogle Scholar
  22. 22.
    Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 2003; 348: 1747–55PubMedCrossRefGoogle Scholar
  23. 23.
    Andrews R, Counahan M, Hogg G, et al. Effectiveness of a publicly funded pneumococcal vaccination program against invasive pneumococcal disease among the elderly in Victoria, Australia. Vaccine 2004; 23: 132–8PubMedCrossRefGoogle Scholar
  24. 24.
    Christenson B, Hedlund J, Lundbergh P, et al. Additive preventive effect of influenza and pneumococcal vaccines in elderly persons. Eur Respir J 2004; 23: 363–8PubMedCrossRefGoogle Scholar
  25. 25.
    Vila-Corcoles A, Ochoa-Gondar O, Hospital I, et al. Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clin Infect Dis 2006; 43(7): 860–8PubMedCrossRefGoogle Scholar
  26. 26.
    Honkanen PO, Keistinen T, Miettinen L, et al. Incremental effectiveness of pneumococcal vaccine on simultaneously administered influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons aged 65 years or older. Vaccine 1999; 17(20–21): 2493–500PubMedCrossRefGoogle Scholar
  27. 27.
    Mykietiuk A, Carratala J, Dominguez A, et al. Effect of prior pneumococcal vaccination on clinical outcome of hospitalized adults with community-acquired pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 2006; 25(7): 457–62PubMedCrossRefGoogle Scholar
  28. 28.
    Sisk JE, Moskowitz AJ, Whang W, et al. Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people. JAMA 1997; 278(16): 1333–9PubMedCrossRefGoogle Scholar
  29. 29.
    Ament A, Baltussen R, Duru G, et al. Cost-effectiveness of pneumococcal vaccination of older people: a study in 5 western European countries. Clin Infect Dis 2000; 31: 444–50PubMedCrossRefGoogle Scholar
  30. 30.
    Melegaro A, Edmunds WJ. The 23-valent pneumococcal polysaccharide vaccine: part II. A cost-effectiveness analysis for invasive disease in the elderly in England and Wales. Eur J Epidemiol 2004; 19: 365–75PubMedCrossRefGoogle Scholar
  31. 31.
    Obaro SK. The new pneumococcal vaccine. Clin Microbiol Infect 2002; 8(10): 623–33PubMedCrossRefGoogle Scholar
  32. 32.
    Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of proteinpolysaccharide conjugate vaccine. N Engl J Med 2003; 348: 1737–46PubMedCrossRefGoogle Scholar
  33. 33.
    Centers for Disease Control and Prevention. Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease: United States, 1998–2003. MMWR Morb Mortal Wkly Rep 2005; 54(36): 893–7Google Scholar
  34. 34.
    Lexau CA, Lynfield R, Danila R, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 2005; 294(16): 2043–51PubMedCrossRefGoogle Scholar
  35. 35.
    Moore MR, Pilishvili T, Bennett NM, et al. Age-specific trends in invasive pneumococcal disease among adults: evidence for indirect effects of conjugate use among children: selected US sites, 1998–2004 [abstract no. PO418]. Fifth International Symposium on Pneumococci and Pneumococcal Diseases; 2006 Apr 2–6; Alice Springs (NT)Google Scholar
  36. 36.
    Lockhart SP, Hackell JG, Fritzell B. Pneumococcal conjugate vaccines: emerging clinical information and its implications. Expert Rev Vaccines 2006; 5(4): 553–64PubMedCrossRefGoogle Scholar
  37. 37.
    Kyaw MH, Lynfield R, Schaffner W, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med 2006; 354: 1455–63PubMedCrossRefGoogle Scholar
  38. 38.
    Fry AM, Zell ER, Schuchat A, et al. Comparing potential benefits of new pneumococcal vaccines with the current polysaccharide vaccine in the elderly. Vaccine 2002; 21: 303–11PubMedCrossRefGoogle Scholar
  39. 39.
    Abraham-Van Parijs B. Review of pneumococcal conjugate vaccine in adults: implications on clinical development. Vaccine 2004; 22(11–12): 1362–71PubMedCrossRefGoogle Scholar
  40. 40.
    Lucero MG, Dulalia VE, Parreno RN, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age. Cochrane Database Syst Rev 2004; (4): CD004977Google Scholar
  41. 41.
    Powers DC, Anderson EL, Lottenbach K, et al. Reactogenicity and immunogenicity of a protein-conjugated pneumococcal oligosaccharide vaccine in older adults. J Infect Dis 1996; 173: 1014–8PubMedCrossRefGoogle Scholar
  42. 42.
    Wuorimaa T, Kayhty H, Leroy O, et al. Tolerability and immunogenicity of an 11-valentpneumococcal conjugate vaccine in adults. Vaccine 2001; 19(15–16): 1863–9PubMedCrossRefGoogle Scholar
  43. 43.
    Jackson LA, Neuzil KM, Whitney CG, et al. Safety of varying dosages of 7-valent pneumococcal protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine 2005; 23(28): 3697–703PubMedCrossRefGoogle Scholar
  44. 44.
    De Roux A, Kuhnke A, Schmole-Thoma B, et al. Immunogenecity, safety and tolerability of a seven valent pneumococcal conjugate (7vPnC) and pneumococcal polysaccharide (23vPnS) vaccine booster dose 12 months after first injection in elderly individuals [abstract no. 980]. Annual Meeting of Infectious Disease Society of America; 2005 Oct 5–9; San Francisco (CA)Google Scholar
  45. 45.
    Shelly MA, Jacoby H, Riley GJ, et al. Comparison of pneumococcal polysaccharide and CRM197-conjugated pneumococcal oligosaccharide vaccines in young and elderly adults. Infect Immun 1997; 65: 242–7PubMedGoogle Scholar
  46. 46.
    Feikin DR, Klugman KP, Facklam RR, et al. Increased prevalence of pediatric pneumococcal serotypes in elderly adults. Clin Infect Dis 2005; 41: 481–7PubMedCrossRefGoogle Scholar
  47. 47.
    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: 1341–8PubMedCrossRefGoogle Scholar
  48. 48.
    Clinical trial: assess the immunogenicity of GSK biologicals’ 10-valent pneumococcal conjugate vaccine [online]. Available from URL: http://www.clinicaltrials.gov/ct/show/NCT00307541 [Accessed 2007 Jan 10]
  49. 49.
    Prymula R, Peeters P, Chrobok V, 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): 740–8PubMedCrossRefGoogle Scholar
  50. 50.
    Wuorimaa TK, Dagan R, Bailleux F, et al. Functional activity of antibodies after immunization of Finnish and Israeli infants with an 11-valent pneumococcal conjugate vaccine. Vaccine 2005; 23(46–47): 5328–32PubMedCrossRefGoogle Scholar
  51. 51.
    Clinical trial: study evaluating pneumococcal vaccine in healthy infants [online]. Available from URL: http://www.clinicaltri-als.gov/ct/show/NCT00205803 [Accessed 2007 Jan 10]
  52. 52.
    Briles DE. Protection of the elderly from pneumococcal pneumonia with a protein-based vaccine? Mech Ageing Dev 2004; 25(2): 129–31CrossRefGoogle Scholar
  53. 53.
    Tai SS. Streptococcus pneumoniae protein vaccine candidates: properties, activities and animal studies. Crit Rev Microbiol 2006; 32(3): 139–53PubMedCrossRefGoogle Scholar
  54. 54.
    Garcia-Suarez MM, Vazquez F, Mendez FJ. Streptococcus pneumoniae virulence factors and their clinical impact: an update. Enferm Infecc Microbiol Clin 2006; 24(8): 512–7CrossRefGoogle Scholar
  55. 55.
    Wu HY, Nahm MH, Guo Y, et al. 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): 839–46PubMedCrossRefGoogle Scholar
  56. 56.
    Arulanandam BP, Lynch JM, Briles DE, et al. Intranasal vaccination with pneumococcal surface protein A and in-terleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection. Infect Immun 2001; 69(11): 6718–24PubMedCrossRefGoogle Scholar
  57. 57.
    Seo JY, Seong SY, Ahn BY, et al. Cross-protective immunity of mice induced by oral immunization with pneumococcal surface adhesin a encapsulated in microspheres. Infect Immun 2002; 70(3): 1143–9PubMedCrossRefGoogle Scholar
  58. 58.
    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(17): 1743–54PubMedCrossRefGoogle Scholar
  59. 59.
    Moore QC, Bosarge JR, Quin LR, et al. Enhanced protective immunity against pneumococcal infection with PspA DNA and protein. Vaccine 2006; 24(29–30): 5755–61PubMedCrossRefGoogle Scholar
  60. 60.
    Ogunniyi AD, Grabowicz M, Briles DE, et al. Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae. Infect Immun 2007; 75(1): 350–7PubMedCrossRefGoogle Scholar
  61. 61.
    Baril L, Briles DE, Crozier P, et al. Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease. Vaccine 2004; 23(6): 789–93PubMedCrossRefGoogle Scholar
  62. 62.
    Baril L, Dietemann J, Essevaz-Roulet M, et al. Pneumococcal surface protein A (PspA) is effective at eliciting T cell-mediated responses during invasive pneumococcal disease in adults. Clin Exp Immunol 2006; 145(2): 277–86PubMedCrossRefGoogle Scholar
  63. 63.
    Linder A, Hollingshead S, Janulczyk R, et al. Human antibody response towards the pneumococcal surface proteins PspA and PspC during invasive pneumococcal infection. Vaccine 2007; 25(2): 341–5PubMedCrossRefGoogle Scholar
  64. 64.
    Kirkham LA, Kerr AR, Douce GR, et al. Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines. Infect Immun 2006; 74(1): 586–93PubMedCrossRefGoogle Scholar
  65. 65.
    Audouy SA, van Roosmalen ML, Neef J, et al. Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization. Vaccine 2006; 24(26): 5434–41PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Department of Public Health, Primary Care Service of Tarragona-VailsInstitut Català de la SalutTarragonaSpain

Personalised recommendations