Estimating the Serotype-Specific Association Between the Concentration of Vaccine-Induced Serum Antibodies and Protection Against Pneumococcal Colonization.

Background: Pneumococcal conjugate vaccines (PCVs) offer indirect protection by reducing pneumococcal colonization in the vaccinated children and thus transmission. As higher-valency PCVs may trigger a weaker immune response, it is important to understand how differences in immunogenicity between PCVs translate to effectiveness against colonization.

Methods: We estimated the serotype-specific relationship between the concentration of vaccine-induced serum immunoglobulin G (IgG) and protection against colonization using a hierarchical Bayesian model with the longitudinal data from a randomized controlled trial. We then combined these estimates with the summary-level immunogenicity data (geometric mean concentrations and 95% confidence intervals) from head-to-head clinical trials comparing 13-valent versus 7-valent PCV (PCV13 vs PCV7), 15-valent PCV (PCV15) versus PCV13, and 20-valent PCV (PCV20) versus PCV13 to infer the relative effectiveness of higher-valency PCVs against colonization.

Results: The hierarchical Bayesian model predicted that the risk of colonization increased as serum IgG decreased, and the association differed by serotype. Our approach estimated higher-valency PCVs to have lower vaccine effectiveness against colonization with some serotypes: 14 and 23F across comparisons; 4 when comparing PCV13 with PCV7 and PCV20 with PCV13; 5, 6A, 6B 7F, 19A, and 19F when comparing PCV15 and PCV20 with PCV13; and 1, 9V, and 18C when comparing PCV20 with PCV13.

Conclusions: These findings suggest that while new PCVs might provide sufficient protection against disease, protection against transmission might be somewhat reduced for some serotypes. The overall impact should be evaluated in the local context, and further monitoring is critical to evaluate the impact of these changes in the coming years.