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.
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.
Authors: Sharavathi Guddehalli Parameswarappa; Katrin Reppe; Andreas Geissner; Petra Ménová; Subramanian Govindan; Adam D J Calow; Annette Wahlbrink; Markus W Weishaupt; Bopanna Ponnappa Monnanda; Roland Lawrence Bell; Liise-Anne Pirofski; Norbert Suttorp; Leif Erik Sander; Martin Witzenrath; Claney Lebev Pereira; Chakkumkal Anish; Peter H Seeberger Journal: Cell Chem Biol Date: 2016-11-03 Impact factor: 8.116