The Safety and Immunogenicity of a Human Immunodeficiency Virus Type 1 (HIV-1) Recombinant gp160 Candidate Vaccine in Humans

doi:10.1059/0003-4819-114-2-119

The Safety and Immunogenicity of a Human Immunodeficiency Virus Type 1 (HIV-1) Recombinant gp160 Candidate Vaccine in Humans

Raphael Dolin, MD;
Barney S. Graham, MD;
Stephen B. Greenberg, MD;
Carol O. Tacket, MD;
Robert B. Belshe, MD;
Karen Midthun, MD;
Mary Lou Clements, MD;
Geoffrey J. Gorse, MD;
Brian W. Horgan, PA;
Robert L. Atmar, MD;
David T. Karzon, MD;
William Bonnez, MD;
Bruce F. Fernie, ScD;
David C. Montefiori, PhD;
Donald M. Stablein, PhD;
Gale E. Smith, PhD;
Wayne C. Koff, PhD; and
NIAID AIDS Vaccine Clinical Trials Network

Abstract

Objective: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp160) candidate vaccine in humans.

Subjects: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups.

Interventions: The subjects were randomly assigned to receive 40 or 80 µg of rgp160,10 µg of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540.

Measurements and Main Results: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum anti-body responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-µg doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 of 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time.

Conclusions: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.

Article and Author Information

From the University of Rochester School of Medicine and Dentistry, Rochester, New York; Vanderbilt University, Nashville, Tennessee; Baylor College of Medicine, Houston, Texas; University of Maryland at Baltimore, Baltimore, Maryland; St. Louis University School of Medicine, St. Louis, Missouri; Johns Hopkins University School of Hygiene and Public Health and School of Medicine, Baltimore, Maryland; Georgetown University, Rockville, Maryland; The Emmes Corporation, Potomac, Maryland; MicroGeneSys, Inc., West Haven, Connecticut; and the NIAID AIDS, Rockville, Maryland. For current author addresses, see end of text.
Grant Support: By contracts (N01-AI-52577, N01-AI-72624, N01-AI-62528, N01-AI-52575, N01-AI-52576, N01-AI-72623, N01-AI-82500, N01-AI-62515) from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Requests for Reprints: Raphael Dolin, MD, Infectious Disease Unit, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 689, Rochester, NY 14642.
Current Author Addresses: Drs. Dolin and Bonnez: University of Rochester Medical Center, 601 Elmwood Avenue, Box 689, Rochester, NY 14642.

Drs. Graham, Karzon, and Montefiori: Vanderbilt University, Medical Center North, Nashville, TN 37232.

Drs. Greenberg and Atmar: Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

Dr. Tacket and Mr. Horgan: University of Maryland, Center for Vaccine Development, 10 South Pine Street, MSTF Building, Baltimore, MD 21201.

Drs. Belshe and Gorse: St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104.

Drs. Midthun and Clements: Johns Hopkins University, Hampton House, 624 North Broadway, Baltimore, MD 21205.

Dr. Fernie: Division of Molecular Virology & Immunology, Georgetown University, 5640 Fishers Lane, Rockville, MD 20852.

Dr. Stablein: The Emmes Corporation, 11325 Seven Locks Road, Suite 214, Potomac, MD 20892.

Dr. Koff: AIDS Program, NIAID, Vaccine Research and Development Branch, 6003 Executive Boulevard, Rockville, MD 20892.