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

doi:10.1128/JVI.75.18.8681-8689.2001

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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 Group

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 type1 (HIV-1) infection, presumably due to effective CD8⁺ cytotoxic T-lymphocyte responses, but close relationships betweenclass I variants mediating such responses to natural and to vaccineHIV-1 antigen have not been established. During 6 to 30 monthsof administration and follow-up in trials of ALVAC-HIV recombinantcanarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinatedsubjects typed at class I loci responded to an HIV-1 protein ina lytic bulk CD8⁺ cytotoxic T-lymphocyte assay. By 2 weeks after the second dose,higher proportions of vaccinees carrying one of two alleles consistentlyassociated with slower progression of natural HIV-1 infectionreacted at least once: B*27 carriers reacted to Gag (64%; oddsratio [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). By2 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*57carriers 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 naturalinfection, showed no such disadvantage for vaccine response. Individualclass I alleles have not previously demonstrated such clear andconsistent relationship with both the clinical course of an infectionand cellular immunity to a vaccine against the infectious agent.This proof of principle that class I an alleles modulate bothprocesses has implications for development of HIV-1 and presumablyothervaccines.

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

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 (Universityof 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.).

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