Summary
Streptococcus pneumoniae (pneumococcus) is a leading cause of devastating bacterial pneumonia and sepsis in children, particularly in LMIC countries. The most effective public intervention to reduce pneumococcal diseases is vaccination. Despite the use of effective polysaccharide-based existing vaccines, pneumococcal disease still affects significant numbers of children worldwide. Underlying this continuing prevalence are (i) increasing cases of disease caused by pneumococcus serotypes not protected by existing vaccines and (ii) very early life infection prior to vaccination.
This window of susceptibility could be reduced by 1: vaccinating mothers to provide children with protection from birth and 2: using novel vaccines that overcome pneumococcal strain replacement (vaccine evasion).
We have already discovered that maternal vaccination with both an existing and a novel mucosal-delivered vaccine candidate provides long term protection to offspring against invasive pneumococcus disease (IPD). This important finding indicates that windows of vulnerability not covered by existing vaccination to IPD could be closed using similar alternative approaches.
This proposed project will use our established preclinical models to test how maternal type 2 immune bias influences development of a protective response to vaccination and subsequent short- and long-term maternal transfer of immunity to offspring. We will specifically address how manipulating maternal immunity at the time of vaccination during pregnancy enhances the efficacy of maternal transfer of protective immunity to offspring against pneumococcal disease. The findings of this work will inform on how vaccines delivered before or during pregnancy can be optimally formulated to transfer high levels of protective immunity to offspring.
Project Outcome
We have found vaccination of mothers against pneumococcal infection protects offspring into adulthood. This is dependent on maternal Type 2 immunity, mothers lacking IL-4Ra transfer reduced protection to offspring. Protection relates to detection of maternal microchimeric plasma cells in offspring.