Positively Selected Codons in Immune-Exposed Loops of the Vaccine Candidate OMP-P1 of <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> |
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Authors: | Ted H M Mes Jos P M van Putten |
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Institution: | (1) Netherlands Institute of Ecology (NIOO-KNAW), Centre for Estuarine and Marine Ecology, P.O.B. 140, 4400, AC, Yerseke, The Netherlands;(2) Department of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584, CL, Utrecht, The Netherlands |
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Abstract: | The high levels of variation in surface epitopes can be considered as an evolutionary hallmark of immune selection. New computational
tools enable analysis of this variation by identifying codons that exhibit high rates of amino acid changes relative to the
synonymous substitution rate. In the outer membrane protein P1 of Haemophilus influenzae, a vaccine candidate for nontypeable strains, we identified four codons with this attribute in domains that did not correspond
to known or assumed B- and T-cell epitopes of OMP-P1. These codons flank hypervariable domains and do not appear to be false
positives as judged from parsimony and maximum likelihood analyses. Some closely spaced positively selected codons have been
previously considered part of a transmembrane domain, which would render this region unsuited for inclusion in a vaccine.
Secondary structure analysis, three-dimensional structural database searches, and homology modeling using FadL of E. coli as a structural homologue, however, revealed that all positively selected codons are located in or near extracellular looping
domains. The spacing and level of diversity of these positively selected and exposed codons in OMP-P1 suggest that vaccine
targets based on these and conserved flanking residues may provide broad coverage in H. influenzae.
Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Reviewing Editor: Dr. Rasmus Nielson] |
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Keywords: | Haemophilus influenzae Outer membrane proteinI Immune selection Structural information Epitope Vaccine |
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