title: Polymorphisms in HLA class I genes associated with both favorable prognosis of human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T-lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines.
abstract: Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8(+) cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8(+) cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B*27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B*57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B*27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P < 0.05) and B*57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.
authors.affiliation: Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. rkaslow@uab.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: C
authors.initials: C
authors.lastname: Rivers
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: T J
authors.initials: TJ
authors.lastname: Bender
authors.forename: P A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: R
authors.initials: R
authors.lastname: El Habib
authors.forename: K
authors.initials: K
authors.lastname: Weinhold
authors.forename: M J
authors.initials: MJ
authors.lastname: Mulligan
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D018150:Avipoxvirus; D004311:Double-Blind Method; D005805:Genes, MHC Class I; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D012309:Risk-Taking; D012725:Sexual Behavior; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D014614:Vaccines, Synthetic