Viral vectors expressing group B meningococcal outer membrane proteins induce strong antibody responses but fail to induce functional bactericidal activity

Leanne Marsay, Christina Dold, Gavin K. Paterson, Yuko Yamaguchi, Jeremy P. Derrick, Hannah Chan, Ian M. Feavers, Martin C.J. Maiden, David Wyllie, Adrian V. Hill, Andrew J. Pollard, Christine S. Rollier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 (>105 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.

Original languageEnglish
Pages (from-to)658-667
Number of pages10
JournalJournal of Infection
Volume84
Issue number5
DOIs
Publication statusPublished - May 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a project grant from Meningitis UK (now MeningitisNow), Wellcome Trust, Innovation Schemes (Ref 082102/Z/07/A and 091634/Z/10/Z), and by the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom, Vaccine theme. The funding sources had no involvement in study design, conduct of research, preparation of the article nor in the decision to submit for publication.

Publisher Copyright:
© 2022

Keywords

  • Adenovirus
  • Meningococcal disease
  • Meningococcus
  • Outer membrane protein
  • Porin
  • Vaccine
  • Vector

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