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

J Virol. 2001 Sep;75(18):8681-9. doi: 10.1128/jvi.75.18.8681-8689.2001.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • Adolescent
  • Adult
  • Alleles
  • Avipoxvirus
  • Double-Blind Method
  • Genes, MHC Class I*
  • Genetic Vectors
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-C Antigens / genetics
  • Haplotypes
  • Homozygote
  • Humans
  • Middle Aged
  • Polymorphism, Genetic*
  • Prognosis
  • Risk Factors
  • Risk-Taking
  • Sexual Behavior
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Synthetic / immunology*

Substances

  • AIDS Vaccines
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Vaccines, Synthetic