3 years ago

Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen.

Pupo E, Houben D, Azarian T, Kuipers K, Langereis JD, Simonetti E, Jong WSP, Zomer A, Luirink J, van Selm S, van Opzeeland F, van der Gaast-de Jongh CE, van der Ley P, de Groot R, de Jonge MI, Koenders MI
Serotype-specific protection against a Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission and limit emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of LPS-detoxified outer membrane vesicles (OMVs) from Salmonella Typhimurium displaying the variable N-terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with substantial reduction of pneumococcal colonization. Despite the variable nature of this protein a common MHCII epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for the IL17A-mediated cross-reactivity and associated with cross-protection. Based on 1352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% strains, illustrating the potential of Th17-mediated cross protection.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28717032

DOI: PubMed:28717032

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