title: Immunogenicity of sequences around HIV-1 protease cleavage sites: potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites.
abstract: Developing an effective preventative vaccine against HIV-1 has proved to be a great challenge. The classical and proven vaccine approach has failed so far or produced a modest effect, new approaches are needed. In this study we evaluated the immunogenicity of the sequences around the protease cleavage sites (PCS) and the population coverage of a vaccine targeting HIV-1 PCS. The sequence conservation was evaluated by comparing entropy score of sequences around PCS with Gag and Pol. The immunogenicity of sequences around the 12 PCS (+10/-10 amino acids) was analyzed by identifying epitopes of HLA class I alleles in PCS region using four approaches: (1) identification of previously reported HLA class I allele epitopes around PCS region; (2) screening and validating epitopes of 8 HLA class I alleles common to most world populations using iTopia Epitope Discovery system and IFN-γ ELISpot assays; (3) screening of 151 patients of Pumwani cohort for PBMC IFN-γ ELISPOT responses to the subtype A and D consensus around PCS region; and (4) prediction of HLA alleles with epitopes around the PCS using NetMHCpan. Population coverage was calculated using the web-based analysis tool of the Immune Epitope Database based on HLA class I genotype frequencies from dbMHC database. The results showed that many HLA class I alleles have multiple epitopes in the 12 PCS regions, indicating sequence immunogenicity around PCS. Multiple epitopes of many HLA class I alleles common to >95% world populations have been identified around the 12 PCS region. Targeting these sites is a feasible vaccine approach.
authors.affiliation: National Microbiology Laboratory, Winnipeg, Manitoba, Canada. Ma_Luo@phac-aspc.gc.ca
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.forename: Rupert
authors.initials: R
authors.lastname: Capina
authors.forename: Christina
authors.initials: C
authors.lastname: Daniuk
authors.forename: Jeff
authors.initials: J
authors.lastname: Tuff
authors.forename: Harold
authors.initials: H
authors.lastname: Peters
authors.forename: Makubo
authors.initials: M
authors.lastname: Kimani
authors.forename: Charles
authors.initials: C
authors.lastname: Wachihi
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Terry Blake
authors.initials: TB
authors.lastname: Ball
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000483:Alleles; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D016333:HIV Protease / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008969:Molecular Sequence Data; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1