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.

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.

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.

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. Competing Interest Statement DMW has received consulting fees from Pfizer, Merck, Affinivax, Matrivax, and GSK and is principal investigator on grants from Pfizer and Merck to Yale University. RD has received grants from Pfizer, MSD, MedImmune/AstraZenaca. He serves as a scientific consultant and on the advisory board of Pfizer and MSD. He is also part of the speakers' bureau of Pfizer, MSD, Sanofi Pasteur, and GSK. SP is principal investigator on grants from Merck to Yale University. The other authors have no conflicts of interest to report. Funding Statement This study was partially supported by a grant from the Bill and Melinda Gates Foundation (Grant no. INV-065870). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The analyses of these de-identified data were exempted from review by the Yale University Institutional Review Boards (Protocol ID: 2000038285). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Analysis code and data from the scoping review are available from: