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Journal of Virology, September 2001, p. 8681-8689, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8681-8689.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Richard A. Kaslow,1,2,* Charles Rivers,1 Jianming Tang,2 Thomas J. Bender,1 Paul A. Goepfert,2 Raphaelle El Habib,3 Kent Weinhold,4 Mark J. Mulligan,2 and the NIAID Aids Vaccine Evaluation Groupdagger

Department of Epidemiology and International Health, School of Public Health,1 and Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 352942; Aventis Pasteur, Marcy l'Etoile, France3; and Duke University Medical Center, Durham, North Carolina 277104

Received 4 January 2001/Accepted 23 June 2001

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.

* Corresponding author. Mailing address: Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, 220A Ryals Building, 1665 University Blvd., Birmingham, AL 35294-0022. Phone: (205) 975-8698. Fax: (205) 934-8665. E-mail: rkaslow{at}uab.edu.

dagger Participants of the NIAID AIDS Vaccine Evaluation Group who contributed to this study include: M. L. Clements-Mann and D. Schwartz (Johns Hopkins University, Baltimore, Md.); R. Belshe, G. Gorse, and S. Frey (St. Louis University School of Medicine, St. Louis, Mo.); R. Dolin, M. Keefer, and T. Evans (University of Rochester Medical Center, Rochester, N.Y.); L. Corey and J. McElrath (University of Washington, Seattle, Wash.); and B. Graham, P. Wright, and P. Spearman (Vanderbilt University, Nashville, Tenn.).

Journal of Virology, September 2001, p. 8681-8689, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8681-8689.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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