The future of pneumococcal disease prevention

Pneumococcal disease (PD) is the leading cause of vaccine preventable deaths in children <5 years of age worldwide, with most of the deaths occurring in the developing world. Prevention of PD in children has been achieved by vaccination with pneumococcal conjugate vaccine (PCV), the basis for which is induction of a protective antibody response against the bacterial polysaccharide capsule. Conjugation of the polysaccharide capsule to a protein carrier enables the generation of an immunologic response to the vaccine in young children, leading to protection against infection. The heptavalent PCV, which contains 7 of the 93 known pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) was the first PCV available, licensed in the US in 2000 and subsequently in many countries worldwide, including Latin American and Caribbean countries. Since its introduction, PCV7 has been documented effective for reducing invasive PD mortality and burden, as well as that of pneumonia and otitis media. Additionally, PD caused by the vaccine serotypes has decreased in the unimmunized population due to herd immunity induced by PCV7. Despite this success, significant disease burden still exists globally due to serotypes not included in PCV7. Currently there are 2 new PCVs that have been approved for use in children, a 10-valent vaccine (includes PCV7 serotypes plus serotypes 1, 5 and 7F) and a 13-valent vaccine (includes PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A). The selection of new serotypes to be included was based on importance of these serotypes as causes of PD. An additional 15-valent vaccine (includes PCV 7 serotypes plus serotypes 1, 3, 5, 6A, 7F, 19A, 22F and 33F) is undergoing clinical trial testing. In view of the 93 serotypes that are currently known, it seems clear that vaccines with greater coverage, likely based on proteins common to all serotypes, will be needed in the future. Technical and regulatory challenges to the development and approval of newer PCVs include a need for licensing criteria of common protein vaccines, establishment of correlates of protection for disease manifestations other than invasive disease, comparative efficacy data, and clinical trial testing of concomitant immunization of higher valency PCVs with other vaccines.