IgG antibody concentrations after immunization with 11-valent mixed-carrier pneumococcal conjugate vaccine in efficacy trial against pneumonia among Filipino infants.

BACKGROUND: Pneumococcal pneumonia is a major cause of morbidity and mortality worldwide. Efficacy of pneumococcal conjugate vaccines (PCV) in reducing childhood pneumonia has been estimated in four double-blind, randomized, controlled trials. An investigational 11-valent pneumococcal conjugate vaccine (11PCV) had an efficacy of 22.9% against radiologically defined pneumonia during first 2 years of life in Filipino infants. We report here the immunogenicity of the vaccine in a nested study of 1111 infants randomized 1:1 to receive 11PCV or placebo scheduled to be given according to the National EPI Program at 6, 10, and 14 weeks of age. METHODS: IgG antibody concentrations to pneumococcal capsular polysaccharides were measured by a standardized enzyme immuno-assay in serum samples drawn post-3rd dose for peak antibody response and at the time of measles vaccination at 9 months of age for persistence of the antibodies. RESULTS: The geometric mean concentrations (GMCs) of antibodies were significantly higher in 11PCV than in placebo recipients against vaccine serotypes at both sampling points. One month post-3rd dose, 93-100% of 11PCV recipients had > or =0.35microg/ml for 9 serotypes, 76% for 6B, and 87% for 23F. The same proportions varied between 24% and 97% at 9.5 months of age due to antibody decrease. GMC to vaccine-related serotype 19A, but not to 6A, was higher in 11PCV than in placebo recipients. 7-12% of the 11PCV recipients had spontaneous antibody increases to serotypes 6B, 23F, and 14 between the two sampling points. These serotypes were common in nasopharyngeal samples of the infants. CONCLUSION: The 11PCV demonstrated good immunogenicity after three doses and persistence of antibodies at least up to 9.5 months of age, comparable to other PCVs that have been evaluated for efficacy against radiologically defined pneumonia in other populations.

Functional antibodies elicited by an 11-valent diphtheria-tetanus toxoid-conjugated pneumococcal vaccine.

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated (r=0.53-0.74) with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.3 (serotype 19F), and 206.3 (serotype 23F). The functionality of antibodies increased after the fourth dose of vaccine (i.e., the concentration required for in vitro killing of pneumococci decreased). Both the quantity and quality of antibodies are important in the evaluation of immunogenicity of pneumococcal vaccines.