AIDSWEEKLY Plus, 11 November 1996
Daniel J. DeNoon, Senior Editor

The vaccine, p24-VLP, contains HIV-1 p17 and p24 core antigens in the form of virus-like particles (VLP) expressed in yeast via a genetically engineered transposon (Ty)/p17/p24 fusion gene. It is being developed by British Biotech Pharmaceuticals Ltd., Oxford, England.

The vaccine has the potential to react with a broad range of HIV strains because the p17 and p24 proteins on which it is modeled come from HIV's interior. Across multiple HIV strains, these core proteins do not change as much as the gp120 and gp160 HIV surface proteins used in many first- generation HIV vaccines.

"Immunization with p24-VLP did not increase anti-p24 antibody levels and had no effect on CD4 cell counts or virus load," wrote Jan Veenstra of the Municipal Health Service, Amsterdam, Netherlands, and colleagues.

Veenstra et al. reported their findings in The Journal of Infectious Diseases ("Immunization with Recombinant p17/p24:Ty Virus-Like Particles in Human Immunodeficiency Virus-Infected Persons," Jour Inf Dis, 1996;174:862-6).

The placebo-controlled, double-blind trial, performed at five sites in the Netherlands and the U.K., enrolled 74 HIV infected, asymptomatic men and women with CD4 counts of more than 350 cells/(micro)L.

All participants had anti-p24 antibodies and lacked HIV p24 antigen.

Subjects were randomized to receive 100, 500, or 1000 (micro)g of p24-VLP with aluminum hydroxide adjuvant or placebo (adjuvant alone) via intramuscular injection at study weeks 0, 4, 8, 12, 16, and 20.

Of the 74 participants, 63 (85 percent) completed the entire series of immunizations and assessments up to week 48. One vaccine recipient (two doses of 100 (micro)g) died suddenly due to causes unrelated to treatment.

Fourfold increases in anti-p24 antibody at any time during follow-up occurred in at least as many of the placebo recipients (5/19) as in any of the vaccine dosage groups (2/18 at 100 (micro)g, 4/19 at 500 (micro)g, 5/18 at 1000 (micro)g).

Fourfold increases in p17 antibody were similar (10/18 at 100 (micro)g, 7/19 at 500 (micro)g, 3/18 at 1000 (micro)g, 4/19 placebo).

However, Ty antibodies were strongly related to dosage and appeared in 17/18 recipients of 1000 (micro)g vaccine but in only one placebo recipient.

Six participants had disease progression, with one advancing to AIDS. All of these individuals received vaccine, but the difference was not statistically significant (P=0.16).

Viral load quantification was performed on four of the placebo recipients and on 10 of the 1000 (micro)g vaccine recipients. Placebo recipients had a slight increase in viral load between entry and week 24; the vaccine recipients had a slight decrease. The difference between groups was not significant (P=0.233).

"In our study, no evidence of a beneficial therapeutic effect or for accelerated immunologic deterioration due to immunization with p24-VLP was found," Veenstra et al. concluded. "No significant changes in laboratory markers for disease progression occurred that could be related to immunization with p24-VLP."

The failure of p24-VLP to increase anti-p24 antibody levels in HIV(+) individuals capable of producing such antibodies was puzzling. A prior study in healthy, HIV negative volunteers showed that the vaccine readily stimulated anti-p24.

"In HIV-1 infected persons the persistent high replication rate of HIV, and the resultant antigenic presentation of core proteins may lead to a humoral immune response that cannot be improved by immunization with exogenous core antigens," Veenstra et al. suggested.

A clinical trial of the p24-VLP vaccine is underway in the U.S.

"The goal of this trial is to induce cellular immunity, specifically, killer T-cells, and to look for evidence that administration of oral or rectal booster doses stimulates antibodies at the mucosal surfaces lining the body entryways," noted NIAID researcher Laurie K. Doepel (NIAID AIDS Agenda, 1995;3).

Primate studies reported in 1994 suggested that mucosal immunization with the simian version of p24-VLP could stimulate three levels of mucosal defenses against simian immunodeficiency virus (SIV).

The p24-VLP used in these studies was covalently linked to the immunogenic cholera toxin B subunit.

"This primate model of noninvasive mucosal immunization establishes an immunological basis for male genital and rectal vaccination in preventing HIV and other sexually transmitted infections during heterosexual or homosexual intercourse," concluded Thomas Lehner of Guy's Hospital, London Bridge, U.K., and colleagues (Lehner et al., J Virol, 1994;68(3):1624- 32).

The corresponding author for this study is Jan Veenstra, Municipal Health Service, Department of Public Health, Room 409, Nieuwe Achtergracht 100, P.O. Box 20244, 1000 HB Amsterdam, Netherlands.

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