Clin Vaccine Immunol. 2017 Jun 21. pii: CVI.00118-17. doi: 10.1128/CVI.00118-17. [Epub ahead of print]

Conjugation of PspA4Pro with capsular Streptococcus pneumoniae polysaccharide serotype 14 does not reduce the induction of cross-reactive antibodies.

da Silva MA1, Converso TR1,2, Gonçalves VM1, Leite LCC1, Tanizaki MM1, Barazzone GC3.

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Current pneumococcal vaccines are composed of bacterial polysaccharides as antigens plain or conjugated to carrier proteins. While efficacious against vaccine serotypes, epidemiologic data shows increasing incidence of infections caused by non-vaccine serotypes of Streptococcus pneumoniae. The use of Pneumococcal surface protein A (PspA) as a carrier protein in a conjugate vaccine could help preventing serotype replacement by increasing vaccine coverage and reducing selective pressure of S. pneumoniae serotypes. PspA is present in all pneumococcal strains, is highly immunogenic and is known to induce protective antibodies. Based on its sequence, PspA has been classified into 3 families and 6 clades. A PspA fragment derived from family 2 clade 4 (PspA4Pro) was shown to generate antibodies with a broad-range of cross-reactivity, across clades and families. Here, PspA4Pro was modified and conjugated to capsular polysaccharide serotype 14 (PS14). We investigated the impact of conjugation on the immune response induced to PspA4Pro and PS14. Mice immunized with the PS14-mPspA4Pro conjugate produced higher titers of anti-PS14 antibodies than the animals that received co-administered antigens. Both conjugated and co-administered PS14 and mPspA4Pro induced antibodies with opsonophagocytic activity against PS14-carrying strain as well as against a panel of strains bearing PspAs from five clades (encompassing families 1 and 2) bearing a non-PS14 serotype. Furthermore, mice immunized with PS14-mPspA4Pro were protected against nasal colonization with a non-related S. pneumoniae strain bearing PspA from clade 1, serotype 6B. These results demonstrate that the cross-reactivity mediated by PspA4Pro is retained following conjugation, supporting the use of PspA4 as a carrier protein in order to enhance pneumococcal vaccine coverage and encourage its further investigation as a candidate in future vaccine designs.

Copyright © 2017 American Society for Microbiology.

PMID: 28637805 DOI: 10.1128/CVI.00118-17