AEGiS-11IAC: Induction of potentially protective immunity in humans with a recombinant subunit HIV-1 vaccine.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Induction of potentially protective immunity in humans with a recombinant subunit HIV-1 vaccine.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. Mo.A.283)
Francis DP, McElrath MJ, Berman PW, Belshe RB, Fast P; Genenvax, South San Francisco, CA, USA. Fax: 415-225-3957. E-mail: francis.don@gene.com.

OBJECTIVE: To induce protective immunity against HIV-1 using a safe vaccine.

METHODS: Two candidate vaccines, one from strain LAI and one from strain MN, consisting of envelope glycoprotein (gp 120) were produced in CHO cells using recombinant DNA technology. Chimpanzees vaccinated with these vaccines were intravenously challenged with LAI and SF-2 (PBMC) respectively. Safety in humans was determined by physical exam and biochemical and hematologic testing following vaccination. Immunogenicity (anti-gp 120, anti-V-3 and neutralizing antibodies) was evaluated post immunization in 561 seronegative adult and infant subjects in 9 separate studies.

RESULTS: Chimpanzees - Two of two chimpanzees immunized with LAI and challenged with LAI were protected. Three of three chimpanzees immunized with MN and challenged with SF2 (PBMC) were protected despite absence of detectable neutralizing antibody to this "primary isolate". All control animals were infected. Humans - After three doses of either 100 micrograms, 300 micrograms, or 600 micrograms of gp 120 given at 0, 1 and 6 months, essentially all recipients tested developed antibodies that bound gp 120 and neutralized three strains of HIV-(MN, LAI and SF2). A fourth dose of vaccine given at 12 or 18 months induced high titer and persistent antibodies. Induction of CTL activity has been rare and inconsistent. Ten of 507 vaccinated adult volunteers have been infected through high-risk behaviors. Characterization of these "breakthrough" viruses has revealed many to be markedly different than the vaccine strain both in genetic sequence and immunologic reactivity.

CONCLUSION: Recombinant gp 120 appears safe and may protect humans from some HIV infections. The extent, breadth, and duration of such protection awaits initiation and completion of efficacy trials.

Keywords: AEGIS, AIDS Vaccines, HIV-1, HIV Infections, Pan troglodytes, Immunity, Vaccines, HIV Seronegativity, Vaccination, Immunity, Active, Animal, Adult, Human, Infant, immunology, ICA11KWDaegis,aidsvaccines,hiv-1,hivinfections,pantroglodytes,immunity,vaccines,hivseronegativity,vaccination,immunity,active,animal,adult,human,infant,immunology,ica11

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MoA283

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.