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 in Israel. Then, we combined these estimates with the summary-level immunogenicity data (geometric mean concentration and 95% confidence intervals) from head-to-head clinical trials comparing PCV13 vs. PCV7, PCV 15 vs. PCV13, and PCV20 vs. 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 comparing PCV20 with PCV13; 5, 6A, 6B 7F, 19A, and 19F when comparing PCV15 and PCV20 with PCV13, and additionally 1, 9V and 18C when comparing PCV20 with PCV13.

Conclusions: These findings suggest that while new PCVs might provide sufficient protection against severe 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.