Viral vectors expressing group B meningococcal outer membrane proteins induce strong antibody responses but fail to induce functional bactericidal activity. Issue 5 (May 2022)

• Record Type: Journal Article
• Authors: Marsay, Leanne; Dold, Christina; Paterson, Gavin K.; Yamaguchi, Yuko; Derrick, Jeremy P.; Chan, Hannah; Feavers, Ian M.; Maiden, Martin C.J.; Wyllie, David; Hill, Adrian V.; Pollard, Andrew J.; Rollier, Christine S.
• Is Part Of: Journal of infection. Volume 84:Issue 5(2022)
• Page Start: 658
• Page End: 667
• Publication Date: 2022-05
• Subjects: Adenovirus -- Vector -- Vaccine -- Outer membrane protein -- Meningococcus -- Meningococcal disease -- Porin; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2022.02.032
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: Meningococcal proteins can be expressed by viral vectored vaccines in mammal cells. The resulting vector-based vaccine candidates are immunogenic in mice. Antibodies against outer membrane proteins reach high titers after a single dose. Antibodies against outer membrane proteins do not have functional capacity. Transmembrane bacterial proteins lose confirmation in vectored vaccines. Summary: Objective: Adenoviral vectored vaccines, with the appropriate gene insert, induce cellular and antibody responses against viruses, parasites and intracellular pathogens such as Mycobacterium tuberculosis . Here we explored their capacity to induce functional antibody responses to meningococcal transmembrane outer membrane proteins. Methods: Vectors expressing porin A and ferric enterobactin receptor A antigens were generated, and their immunogenicity assessed in mice using binding and bactericidal assays. Results: The viral vectors expressed the bacterial proteins in an in vitro cell-infection assay and, after immunisation of mice, induced higher titres (>10 5 end-point titre) and longer lasting (>32 weeks) transgene-specific antibody responses in vivo than did outer membrane vesicles containing the same antigens. However, bactericidal antibodies, which are the primary surrogate of protection against meningococcus, were undetectable, despite different designs to support the presentation of the protective B-cell epitopes. Conclusion: These results demonstrate that, while the transmembrane bacterial proteins expressed by the viral vector induced strong and persistent antigen-specific antibodies, this platform failed to induce bactericidal antibodies. The results suggest that conformation or post-translational modifications of bacterial outer membrane antigens produced in eukaryote cells might not result in presentation of the necessary epitopes for induction of functional antibodies.