Serotypes 22F and 33F have been added to a new 15-valent pneumococcal-conjugate vaccine (V114, Merck) because of their prevalence causing IPD. An effectiveness study to prove disease prevention for pneumococcal strains expressing 22F and/or 33F capsule would be challenging due to sample size required. A possible solution may be to demonstrate a serologic correlate of protection (COP) based on natural disease responses.
We evaluated anti-polysaccharide 22F and 33F antibody levels in 6-36 month old children before and after AOM infections caused by pneumococcal strains expressing 22F or 33F capsule. COP levels were inferred using generalized-linear models. To validate our approach testing of anti-19A and 6A antibody levels as comparators is underway.
The contribution of antibody level to AOM risk was statistically significant for 22F (p=0.014) and 33F (p=0.006). We derived that a level of antibody=0.25µg/ml is a COP threshold for prevention of pneumococcal AOM infections caused by 22F and 33F strains. Among unvaccinated children 18-months olds, 62.5% had titers that exceeded this threshold for 22F.
We conclude that a level of antibody of 0.25μg/ml for 22F and 33F will be effective for preventing AOM in children if such levels are produced in response to V114.