Peer-Reviewed Journal Details
Mandatory Fields
Fitzpatrick, DA;Creevey, CJ;McInerney, JO
2005
July
Journal of Molecular Evolution
Evidence of positive Darwinian selection in putative meningococcal vaccine antigens
Published
9 ()
Optional Fields
AMINO-ACID SITES HUMAN INFLUENZA-VIRUS NEISSERIA-MENINGITIDIS NEGATIVE SELECTION MAXIMUM-LIKELIHOOD ADAPTIVE EVOLUTION GROUP-B PROTEIN GENE RECOMBINATION
61
90
98
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 antoimmunity. 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.
NEW YORK
0022-2844
10.1007/s00239-004-0290-6
Grant Details