Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate vaccine in Gambian infants

Background. Invasive pneumococcal disease is a major cause of mortality and morbidity in young children in developing countries. Pneumococcal polysaccharide/protein conjugate vaccines, which are likely to be immunogenic in the very young, offer a potential way for preventing these infections. Therefore a pilot safety and immunogenicity study of a five-valent conjugate vaccine has been undertaken in an area of rural Africa where invasive pneumococcal disease is prevalent. Methods. Thirty Gambian infants were vaccinated with 3 doses of a five-valent pneumococcal conjugate vaccine containing 5 mu g of type 6B, 14, 18, 19F and 23F polysaccharides conjugated to the diphtheria toxin mutant protein CRM(197) at the ages of 2, 3 and 4 months; 30 infants received 2 doses at the ages of 2 and 4 months and 30 infants who received three doses of a Haemophilus influenzae type b vaccine acted as controls. Local and systemic reactions were recorded after vaccination and antibody titers were measured by an enzyme-linked immunosorbent assay. Results. No serious local or systemic reactions to vaccination were recorded. Antibody responses to each component of the vaccine were demonstrated. One month after immunization with three doses of vaccine, antibody titers were 3 to 11 times higher than before vaccination (postvaccination titers ranged from 2.49 mu g/ml for type 19 polysaccharide to 7.59 mu g/ml for type 14). Elevated titers were well-maintained during the subsequent 4 months. Three doses of vaccine induced higher titers than did two doses. Antibody titers increased 2- to 3-fold over the period of immunization in children who received H. influenzae type b vaccine. Conclusions. A five-valent pneumococcal conjugate vaccine proved safe and immunogenic in Gambian infants. However. a vaccine containing a larger number of serotypes will be necessary to achieve a maximal clinical impact.