AIDSWEEKLY Plus, 18 March 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

Despite receiving four doses of an experimental HIV-1 vaccine, a clinical trial participant became infected with the AIDS virus.

This is the first breakthrough HIV infection in clinical trials of the vaccine being developed by United Biomedical Inc., Hauppauge, New York. Breakthrough infections previously occurred in some participants in early clinical trials of HIV gp120 subunit vaccines.

Neither the UBI nor the subunit vaccines contained live virus. The vaccines were not the source of infection.

Researcher James Kahn of the University of California, San Francisco, reported the breakthrough infection in a presentation of study results at the Eighth Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS, held February 11-15, 1996, in Bethesda, Maryland.

While the breakthrough infection is a setback for the UBI vaccine, it occurred in a trial designed to test safety and immunogenicity - not efficacy - using a prototype vaccine.

This vaccine employs a unique lysine core to which eight HIV peptides can be attached, forming radial octamers. The prototype vaccine contains eight peptides derived from the V3 domain of the MN strain of HIV-1. Future vaccines could use peptides from various representative HIV-1 strains.

Kahn reported that 24 volunteers entered the study. Half received 100 (micro)g of protein (Group A) and half received 500 (micro)g of protein (Group B). Two participants in each group were randomized to receive placebo. Injections were given on days 0, 28 and 168.

Sixteen to 18 weeks after entering the study, 10 subjects in each group received a fourth immunization. One subject in each group was randomized to receive a placebo inoculation.

None of the trial participants developed any significant laboratory or clinical toxicities, and the injections were well tolerated.

Prior to the fourth vaccine injection, geometric mean titers of HIV neutralizing antibody had a value of 28 in the nine Group A vaccine recipients and a value of 17 in the nine Group B vaccine recipients.

After receiving the fourth injection, geometric mean titers of HIV neutralizing antibody in Group A subjects measured 79 at 2 weeks, 134 at 8 weeks, and 58 at 26 weeks.

In contrast, geometric mean titers of HIV neutralizing antibody in Group B subjects measured 166 at 2 weeks, 263 at 8 weeks, and 220 at 26 weeks.

However, the subject who developed HIV infection was a Group B participant who had received all four injections, Kahn noted.

At the November 1993 NIAID Conference on Advances in AIDS Vaccine Development, UBI researchers reported that serum from animals immunized with mixtures of synthetic peptides representing different serotypes of HIV-1 could neutralize globally diverse clinical isolates of HIV-1.

"The AIDS vaccine research community considered these UBI findings to be an important milestone towards the development of an effective AIDS vaccine, since recent epidemiological data have revealed multiple serotypes of HIV-1 now circulating concomitantly in several regions of the world," said Wayne C. Koff, UBI vice president for vaccine research and development. "In addition, UBI demonstrated that a simplified first-generation version of its multicomponent synthetic peptide AIDS vaccine stimulated similar antibodies in animals and, more importantly, in human volunteers from Phase I clinical trials."

The prototype vaccine represents only the clade B isolates common in North America and Western Europe.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.