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    Evidence of Positive Darwinian Selection in Putative Meningococcal Vaccine Antigens


    Fitzpatrick, David A. and Creevey, Christopher J. and McInerney, James O. (2005) Evidence of Positive Darwinian Selection in Putative Meningococcal Vaccine Antigens. Journal of Molecular Evolution, 61 (1). pp. 90-98. ISSN 0022-2844

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    Abstract

    Meningococcal meningitidis is a life-threatening disease. In Europe and the United States the majority of cases are caused by virulent meningococcal strains belonging to serogroup B. Presently there is no effective vaccine against serogroup B strains, as traditional vaccine antigens such as polysaccharide capsules are unusable as they lead to autoimmunity. The year 2000 saw the publication of the complete genome of Neisseria meningitidis MC58, a virulent serogroup B bacterium. Working in conjunction with the sequencing project, researchers endeavored to locate highly conserved membrane-associated proteins that elicit an immune response. It is hoped that these proteins will provide a basis for novel vaccines against serogroup B strains. A number of potential vaccine antigens have been located and are presently in phase I clinical trials. Recently many reports pertaining to the evidence of positive Darwinian selection in membrane proteins of pathogens have been reported. This study utilized in silico methods to test for evidence of historical positive Darwinian selection in seven such vaccine candidates. We found that two of these proteins show signatures of adaptive evolution, while the remaining proteins show evidence of strong purifying selection. This has significant implications for the design of a vaccine against serogroup B strains, as it has been shown that vaccines that target epitopes that are under strong purifying selection are better than those that target variable epitopes.

    Item Type: Article
    Additional Information: Cite as: Fitzpatrick, D.A., Creevey, C.J. & McInerney, J.O. J Mol Evol (2005) 61: 90. https://doi.org/10.1007/s00239-004-0290-6
    Keywords: Neisseria meningitidis; Positive selection; Vaccine design;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11064
    Identification Number: https://doi.org/10.1007/s00239-004-0290-6
    Depositing User: David Fitzpatrick
    Date Deposited: 19 Sep 2019 16:08
    Journal or Publication Title: Journal of Molecular Evolution
    Publisher: Springer Verlag
    Refereed: Yes
    URI:

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