Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus

Sheerin, D; Dold, C; Silva-Reyes, L; Linder, A; Pollard, AJ; Rollier, CS

Author(s): Sheerin, D; Dold, C; Silva-Reyes, L; Linder, A; Pollard, AJ; Rollier, CS;
Details: Publication Year 2022-06-11,Volume 12,Issue #1,Page 86
Journal Title: Cell & Bioscience
Abstract: BACKGROUND: Disease caused by the capsular group B meningococcus (MenB) is the leading cause of infectious death in UK infants. A novel adenovirus-based vaccine encoding the MenB factor H binding protein (fHbp) with an N-terminal dual signal sequence induces high titres of protective antibody after a single dose in mice. A panel of N-terminal signal sequence variants were created to assess the contribution of components of this sequence to transgene expression kinetics of the encoded antigen from mammalian cells and the resultant effect on immunogenicity of fHbp. RESULTS: The full-length signal sequence (FL SS) resulted in superior early antigen expression compared with the panel of variants, as measured by flow cytometry and confocal imaging, and supported higher bactericidal antibody levels against the expressed antigen in mouse sera < 6 weeks post-immunisation than the licensed four component MenB vaccine. The FL SS also significantly increased antigen-specific T cell responses against other adenovirus-encoded bacterial antigens in mice. CONCLUSIONS: These findings demonstrate that the FL SS enhances immunogenicity of the encoded antigen, supporting its inclusion in other viral vectored bacterial antigen transgenes.
Publisher: BMC
Keywords: Expression kinetics; Meningococcal disease; Signal sequence; Transgene; Viral vector vaccines
Research Division(s): Infectious Diseases And Immune Defence
PubMed ID: 35690803
Publisher's Version: https://doi.org/10.1186/s13578-022-00809-3
Open Access at Publisher's Site: https://doi.org/10.1186/s13578-022-00809-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-06-17 09:28:54

Last Modified: 2022-06-17 09:58:52