University of Leicester
Browse
journal.pone.0051045.pdf (492.22 kB)

Construction of Opa-Positive and Opa-Negative Strains of Neisseria meningitidis to Evaluate a Novel Meningococcal Vaccine

Download (492.22 kB)
journal contribution
posted on 2015-07-02, 08:53 authored by C. D. Bayliss, M. Sadarangani, J. C. Hoe, M. J. Callaghan, C. Jones, K. Makepeace, H. Daniels-Treffandier, M. E. Deadman, A. J. Pollard, H. Chan, I. Feavers, P. van der Ley
Neisseria meningitidis is a major global pathogen causing invasive disease with a mortality of 5–10%. Most disease in developed countries is caused by serogroup B infection, against which there is no universal vaccine. Opacity-associated adhesin (Opa) proteins are major meningococcal outer membrane proteins, which have shown recent promise as a potential novel vaccine. Immunisation of mice with different Opa variants elicited high levels of meningococcal-specific bactericidal antibodies, demonstrating proof in principle for this approach. Opa proteins are critical in meningococcal pathogenesis, mediating bacterial adherence to host cells, and modulating human cellular immunity via interactions with T cells and neutrophils, although there are conflicting data regarding their effects on CD4+ T cells. We constructed Opa-positive and Opa-negative meningococcal strains to allow further evaluation of Opa as a vaccine component. All four opa genes from N. meningitidis strain H44/76 were sequentially disrupted to construct all possible combinations of N. meningitidis strains deficient in one, two, three, or all four opa genes. The transformations demonstrated that homologous recombination of exogenous DNA into the meningococcal chromosome can occur with as little as 80 bp, and that minor sequence differences are permissible. Anti-Opa bactericidal antibody responses following immunisation of mice with recombinant Opa were specific to the Opa variant used in immunisation. No immunomodulatory effects were observed when Opa was contained within meningococcal outer membrane vesicles (OMVs), compared to Opa-negative OMVs. These observations support the incorporation of Opa in meningococcal vaccines.

History

Citation

PLoS One, 2012, 7 (12), p. e51045

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Genetics

Version

  • VoR (Version of Record)

Published in

PLoS One

Publisher

Public Library of Science

issn

1932-6203

Copyright date

2012

Available date

2015-07-02

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051045

Notes

Correction available at http://journals.plos.org/plosone/article?id=10.1371/annotation/900641dd-0b06-4a77-9e2c-b7161dd49e1d published 2013-Oct-1.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC