Evidence of positive Darwinian selection in putative meningococcal vaccine antigens.
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.
Fitzpatrick
David A
DA
Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
Creevey
Christopher J
CJ
McInerney
James O
JO
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D017124:Conserved Sequence; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D016013:Likelihood Functions; D022401:Meningococcal Vaccines / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology; D010802:Phylogeny; D011995:Recombination, Genetic; D012641:Selection, Genetic
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines