Prevention of pneumococcal disease through vaccination

Abstract

The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide—more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only short-lived protection. The conjugation of capsular polysaccharides to a protein carrier provides an antigenic complex in a form that can be presented to the immune system and thus recruit antigen specific CD4+ cells (T-dependent antibody). Pneumococcal conjugate vaccines (PCVs), comprising pneumococcal polysaccharides conjugated to a protein carrier, not only induce antibodies but also prime the immune system for protective memory response. These vaccines provide protection in children below 2 years of age, generate long-term protection (highly specific IgG antibodies), generate herd immunity (indirect protection of nonimmunized individuals) and have demonstrated effectiveness in regions that have incorporated them into the national immunization schedules. Global implementation of PCVs has contributed to substantial progress toward reducing childhood mortality, but increased vaccine uptake in developing regions such as Latin America and the Caribbean is necessary to continue toward accomplishing the goals outline in the MDGs.