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

Abstract

BackgroundDisease 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.ResultsThe 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.ConclusionsThese findings demonstrate that the FL SS enhances immunogenicity of the encoded antigen, supporting its inclusion in other viral vectored bacterial antigen transgenes.

An adenoviral-vectored vaccine confers seroprotection against capsular group B meningococcal disease

“…Moreover, although it is expected that the expressed fHbp is glycosylated because of the presence of the tPA (which may cause issues for bacterial antigens in this type of vaccine platform), we do not know whether it would be lapidated. The contribution of each element in the signal sequence has been explored separately ( 47 ).…”