Candidate Vaccine Sequences to Represent Intra- and Inter-Clade HIV-1 Variation 英文参考文献.docVIP

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Candidate Vaccine Sequences to Represent Intra- and Inter-Clade HIV-1 Variation 英文参考文献.doc

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Candidate Vaccine Sequences to Represent Intra- and Inter-Clade HIV-1 Variation 英文参考文献

CandidateVaccineSequencestoRepresentIntra-and Inter-CladeHIV-1Variation OttoO.Yang1,2,3 * 1DivisionofInfectiousDiseases,DepartmentofMedicine,DavidGeffenSchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesof America, 2Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California,UnitedStatesofAmerica,3UCLAAIDSInstitute,LosAngeles,California,UnitedStatesofAmerica Abstract A likely key factor in the failure of a HIV-1 vaccine based on cytotoxic T lymphocytes (CTL) is the natural immunodominance ofepitopesthatfallinvariableregionsoftheproteome,whichbothincreasesthechanceofepitope sequence mismatch with the incoming challenge strain and replicates the pathogenesis of early CTL failure due to epitopeescapemutationduringnaturalinfection. Toidentify potential vaccinesequences tofocustheCTLresponse on highly conserved epitopes, thewholeproteomes ofHIV-1clades A1,B,C,andDwereassessed forShannon entropy at eachaminoacidposition.Highlyconserved regionsinGag(cGag-1,Gag148–214, andcGag-2,Gag253–331), Env(cEnv, Env521–606), andNef(cNef,Nef106–148) wereidentified acrossclades. Inter-andintra-clade variability ofaminoacids within the regions tended to overlap, suggesting that polyvalent representation of consensus sequences for the four clades would allow broad HIV-1 strain representation. These four conserved regions were rich in both known and predicted CTLepitopes presented byabreadth ofHLAtypes, andscreening of54persons withchronic HIV-1infection revealed that these regions are commonly immunogenic in the context of natural infection. These data suggest that vaccine delivery ofa16-valent mixture ofthese regions could focus theCTL response against conserved epitopes that are broadly representative of circulating HIV-1 strains. Citation: Yang OO (2009) Candidate Vaccine Sequences to Represent Intra- and Inter-Clade HIV-1 Variatio