4.7 Article

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

期刊

JOURNAL OF INFECTION
卷 84, 期 5, 页码 658-667

出版社

W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2022.02.032

关键词

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

资金

  1. MeningitisNow
  2. Wellcome Trust [082102/Z/07/A, 091634/Z/10/Z]
  3. NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
  4. Wellcome Trust [082102/Z/07/A, 091634/Z/10/Z] Funding Source: Wellcome Trust

向作者/读者索取更多资源

Adenoviral vectored vaccines can induce cellular and antibody responses against viruses, parasites, and intracellular pathogens. However, while these vaccines can generate strong and persistent antigen-specific antibodies, they fail to produce bactericidal antibodies, potentially due to the inability of bacterial outer membrane antigens produced in eukaryote cells to present the necessary epitopes.
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. Crown Copyright (C) 2022 Published by Elsevier Ltd on behalf of The British Infection Association. All rights reserved.

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