Serum antibody levels to pneumococcal polysaccharides 22F, 33F, 19A and 6A that correlate with protection from colonization and acute otitis media in children

Abstract

BackgroundSerotypes 22F and 33F have been added to a new pneumococcal-conjugate vaccine (PCV-15) because of their prevalence in causing invasive pneumococcal diseases (IPD). MethodWe measured anti-polysaccharide 22F, 33F, 19A and 6A antibodies in children before and after pneumococcal colonization and acute otitis media (AOM) episodes caused by these specific-serotypes. A two-step method for construction of correlate of protection (COP) models included using a generalized estimating equation for the relationship between antibody level, age and colonization history followed by logistic-regression modelling that included colonization or AOM episodes as independent variables, and age adjusted antibody level as the predictor. ResultsA vaccine-induced serum antibody level of 0.45 μg/ml for 22F, 0.51 μg/ml for 6A and 4.1 μg/ml for 19A correlated with prevention of pneumococcal colonization by respective serotypes (insufficient number of cases for 33F to find COP against colonization). Antibody levels of 0.25 μg/ml for 22F, 33F and 6A and 2 μg/ml for 19A correlated with prevention of AOM by the respective serotypes. ConclusionsA COP threshold of anti-22F, 33F, 19A and 6A serum antibodies for NP colonization and AOM in young children can be derived using GEE and logistic regression modelling.