Naturally-induced serum antibody levels in children to pneumococcal polysaccharide 15B that correlate with protection from nasopharyngeal colonization but anti-serotype 15B antibody has low functional cross-reactivity with serotype 15C

Abstract

BackgroundSerotypes 15B and 15C have been added to new different pneumococcal-conjugate vaccines (PCV20 and V116, respectively). We determined a serum anti-15B antibody level that would be a correlate of protection (COP) against nasopharyngeal colonization and assessed functional cross-reactivity against serotype 15B and 15C in children following natural immunization. MethodIgG-antibody to serotype 15B polysaccharide was measured by ELISA in 341 sera from 6 to 36 month old children collected before, at the time of, and after pneumococcal colonization caused by serotypes 15B and 15C. 155 age-matched controls who had no detected colonization caused by serotype 15B or 15C strains were used as controls. A two-step method was used for construction of COP models: a generalized estimating equation followed by logistic-regression. Opsonophagocytic (OPA) assays assessed functional cross-reactivity between serotypes 15B and 15C. ResultsThe derived COP for prevention of colonization was 1.18 µg/ml for serotype 15B and 0.63 µg/ml for serotype 15C, with a predictive probability of 80 %. Antibody levels did not correlate with OPA titers. 30 % of child samples, with moderate to high amounts of ELISA-measured antibody, showed no OPA titer against either serotype 15B or 15C. For remaining samples, very low or no functional cross-reactivity between serotypes 15B and 15C was measured. ConclusionsA COP for prevention of colonization in young children based on naturally-induced antibody levels was derived for serotypes 15B and 15C that differed. Antibody levels correlated poorly with OPA titers and low functional cross-reactivity between serotypes 15B and 15C in child sera was observed.