Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics

Abstract

Background In contrast to the other vaccine serotypes, no protection could be demonstrated in the POET study against serotype 3 acute otitis media (AOM) following primary and booster vaccination with a multi-valent pneumococcal conjugate vaccine. Methods AOM efficacy and immunogenicity data were reviewed. Pheno- and genotypic characteristics of different serotype 3 strains including efficacy study AOM isolates were evaluated. Results Evaluation of vaccine efficacy before and after booster vaccination indicated that lack of efficacy against serotype 3 pneumococci might have been due to declined protection following the booster dose. However, although atypical immunogenicity was observed for serotype 3 in the second year of life, the capacity to respond to serotype 3 plain polysaccharide was not impaired. All but one of the serotype 3 strains examined had abundant polysaccharide capsules. Comparison of serotype 3 capsular polysaccharide biosynthesis gene sequences found no relevant differences between any of the serotype 3 strains, but mRNA transcript levels were lower for the less densely encapsulated strain. Conclusion Lack of clinical efficacy against serotype 3 AOM following pneumococcal conjugate vaccination may be due to an impaired induction of immune memory. A possible alternative explanation may lie with the atypically abundant expression of capsular polysaccharide which could make serotype 3 strains less susceptible to anti-polysaccharide antibody defence mechanisms in the middle ear. The occurrence of acapsular forms during biofilm growth may also play a role. Clinical impact against otitis media, of vaccines containing pneumococcal serotype 3 components, remains unclear until further investigations have demonstrated the value.