Immunization and Pneumococcal Infection

by

Marina Ulanova

• LAST REVIEWED: 15 December 2016
• LAST MODIFIED: 26 August 2014
• DOI: 10.1093/obo/9780199756797-0136

Introduction

Streptococcus pneumoniae, or pneumococcus, is an important bacterial pathogen responsible for serious communicable diseases such as pneumonia, meningitis, and sepsis, mainly affecting young children and the elderly. According to World Health Organization (WHO) estimates, pneumococcus caused 476,000 deaths of children below the age of 5 years worldwide in 2008. The highest case-fatality rates are found in developing countries, where up to 50 percent of young children who develop pneumococcal meningitis can die. Invasive pneumococcal disease (IPD) is defined as a condition when pneumococcus is isolated from sterile body sites such as blood or cerebrospinal fluid; IPD represents the most serious form of this infection. Pneumococcus can also cause less severe disease, such as otitis media or sinusitis; moreover, it can be asymptomatically carried by normal individuals in the upper airways. The polysaccharide capsule surrounding pneumococcus is the major virulence factor, and antibodies specific to the capsule is the principal defense mechanism against the infection. As young children do not have anticapsular polysaccharide antibodies, they are highly susceptible to pneumococcal infection. The elderly, as well as certain categories of individuals with host defense defects, such as primary immunodeficiency, HIV infection, or asplenia, are also vulnerable. Prevention of pneumococcal infection can be achieved through immunization with polysaccharide antigens that will result in the production of protective antibodies. However, there are two major issues with pneumococcal immunization. First, pneumococcus exists in multiple antigenic variants; indeed, there are more than ninety serological types (serotypes) that differ in antigenic properties of the capsular polysaccharides. Since it is not possible at this time to immunize against all the serotypes, the existing vaccines contain capsular polysaccharides of the most prevalent and virulent serotypes, such as 23, 13, or 10 antigens, depending on vaccine formulation. The second issue is that capsular polysaccharides are not immunogenic in children below the age of two years, when humans are most susceptible to pneumococcal infection. Bacterial capsular polysaccharides are T-cell independent antigens, and antibody production critically depends on a specific B-cell subpopulation, which develops in humans after two years of age. To overcome this issue of low immunogenicity of pneumococcal polysaccharides in young children, protein-polysaccharide conjugate vaccines are used for pediatric immunization. In such vaccines, pneumococcal polysaccharides acquire properties of T-cell dependence and they are consequently immunogenic in infants. Currently, two different types of pneumococcal vaccines are available: a 23-valent pneumococcal polysaccharide vaccine, and two conjugate vaccines (13-valent and 10-valent). The latter vaccines are replacing a previously used 7-valent conjugate vaccine.

Textbooks and Reviews

A large number of textbooks and review articles are available that describe various aspects of pneumococcal infection as well as immunization principles to prevent the disease, covering epidemiology, characteristics of the pathogen, existing pneumococcal vaccines, and issues related to the evolving features of the pathogen under current immunization and antibiotic therapy pressure. Only a few recent resources are included in this section, representing an essential reading list on the subject. Tuomanen 2004 is a great introductory reading covering all essential aspects of this infection, including basic science data and historical perspective on the subject. As a more clinically oriented resource, Musher 2010, an entry in a book on infectious diseases, is helpful for both clinicians and public health professionals. Klugman, et al. 2013 and Jackson 2013, two chapters from the book Vaccines (edited by Stanley Plotkin, Walter Orenstein, and Paul Offit), give a comprehensive overview of two major types of pneumococcal vaccines. Klugman, et al. 2013 has a specific focus on pneumococcal conjugate vaccines, including the most recent research and development information in this field, and also provides essential background that helps to understand fundamental issues with vaccine immunogenicity, efficacy, and potential drawbacks. Jackson 2013 describes various aspects of pneumococcal polysaccharide vaccines. American Academy of Pediatrics 2012 provides more specific information on the clinical application of pneumococcal vaccines for pediatricians. Atkinson, et al. 2009 is also an application-oriented book, but it covers both pediatric and adult immunization, including groups at high risk for pneumococcal infection. World Health Organization 2009, a review on global epidemiology, summarizes data on the pneumococcal disease burden in children, covering both pre-vaccine and post-vaccine time, with an emphasis on vaccine impact in developed and developing countries.

• American Academy of Pediatrics. 2012. Pneumococcal infections. In Red Book: 2012 report of the Committee on Infectious Diseases. 28th ed. Edited by L. K. Pickering, D. W. Kimberlin, and S. S. Long, 571–582. Elk Grove Village, IL: American Academy of Pediatrics.

  NNNThis book, prepared by the American Academy of Pediatrics, is designed to provide essential information on vaccine-preventable diseases and current immunization guidelines relevant to clinical practice; it is regularly updated to include all the recent information on immunization.

• Atkinson, W., S. Wolfe, J. Hamborsky, and L. McIntyre, eds. 2009. Epidemiology and Prevention of Vaccine-Preventable Diseases. 11th ed. Atlanta, GA: Centers for Disease Control and Prevention.

  NNNThis book is produced by the Education, Information and Partnership Branch, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention. A valuable source for researchers and officers in the public health area.

• Jackson, Lisa A. 2013. Pneumococcal polysaccharide vaccines. In Vaccines. 6th ed. Edited by Stanley Plotkin, Walter Orenstein, and Paul Offit, 542–572. Edinburgh: Elsevier/Sounders.

  NNNComprehensive review of pneumococcal polysaccharide vaccines, including historical data, vaccine immunogenicity, and indications. This chapter contains a summary of clinical trials done in various categories of adults and children, including groups at risk of invasive pneumococcal disease, with vaccine efficacy and effectiveness data.

• Klugman, Keith P., Steven Black, Ron Dagan, Richard Malley, and Cynthia G. Whitney. 2013. Pneumococcal conjugate vaccine and pneumococcal common protein vaccines. In Vaccines. 6th ed. Edited by Stanley Plotkin, Walter Orenstein, and Paul Offit, 504–541. Edinburgh: Elsevier/Sounders.

  NNNThis chapter provides essential information on pneumococcal polysaccharide-protein conjugates that are widely used for current immunization against pneumococcal infection. An issue of serotype replacement resulting from increasing prevalence of non-vaccine serotypes is discussed.

• Musher, Daniel M. 2010. Pneumococcal infections. In Harrison’s infectious diseases. Edited by Dennis L. Kasper and Anthony S. Fauci, 374–384. New York: McGraw-Hill Medical.

  NNNThis is a valuable source for medical students, physicians, and public health/infectious disease control personnel. The chapter provides essential information on pneumococcal infection and its prevention.

• Tuomanen, Elaine I. 2004. The pneumococcus. Washington, DC: ASM Press.

  NNNA comprehensive textbook on pneumococcus and pneumococcal infection that provides both current research data and historical information. A valuable source of information for graduate and medical school students, as well as for infectious disease specialists.

• World Health Organization. 2009. Global literature review of Haemophilus influenzae type b and Streptococcus pneumoniae invasive disease among children less than 5 years of age, 1980–2005. Geneva, Switzerland: World Health Organization.

  NNNA comprehensive review of literature published between January 1980 and December 2005 on the global invasive pneumococcal disease burden in children, prepared by World Health Organization Department of Immunization, Vaccines and Biologicals. A total of 211 studies are summarized.