Vaxgen

AIDSVAX DESCRIPTION

AIDSVAX® is the trade name for all formulations of VaxGen’s preventive HIV/AIDS vaccine. AIDSVAX, which is currently in Phase III clinical trials, is not a treatment for AIDS or HIV. It is meant to prevent infection in people who have not been exposed to the virus. Unlike many earlier vaccines that used live or attenuated virus to trigger an immune response, AIDSVAX is made of synthetic proteins cloned from gp120 and contains no genetic material. It is therefore incapable of causing HIV or AIDS.

Although a typical exposure to HIV involves thousands of viral particles, only a few, perhaps one to 10, result in productive infection. If this were the first exposure, the body’s immune system would be caught off guard by the foreign invaders. Before it could mount an effective response to neutralize the virus particles, HIV would have begun to infect human cells and rapidly multiply. Slowly the virus spreads, eventually overwhelming the immune system.

But a different scenario unfolds if the immune system is primed to recognize the virus and is prepared to mount an effective and rapid response to the initial HIV exposure. In that case, the immune system would neutralize the viral particles before they had a chance to begin their replication process. That’s the principle behind AIDSVAX as well as the one that was used in successful vaccines against polio, smallpox, herpes and hepatitis B, among other diseases.

The primary ingredient in AIDSVAX is a synthetic version of gp120, the surface protein of HIV that binds to human cells. While this synthetic protein is incapable of causing HIV infection, it nevertheless prompts the immune system to produce antibodies to gp120. It’s as if the immune system were put through an extensive training exercise. In the event of an exposure to HIV, the immune system quickly recognizes the invader and produces antibodies designed to coat gp120. Encumbered by antibodies, the virus would be unable to enter human cells and replicate, dying off within a few hours in the bloodstream.

AIDSVAX is manufactured for us by Genentech, Inc., which has developed a proprietary method for producing synthetic gp120. Using recombinant DNA technology, gp120 is cloned from HIV into Chinese hamster ovary cells, which act as cellular factories to produce commercial quantities of the synthetic version. We have an exclusive license from Genentech to all the technical know-how and genetic material required to produce synthetic gp120.

SCIENTIFIC PROGRESS

Scientific Milestones to Developing AIDSVAX®

This section summarizes articles that support the scientific rationale for AIDSVAX® and VaxGen’s Phase III trials. The first five appeared in scientific journals, and the final two were presentations made at the 13th International AIDS Conference in Durban, South Africa in July 2000.

Protection of MN-rgp-Immunized Chimpanzees from Heterologous Infection with a Primary Isolate of Human Immunodeficiency Virus Berman, et al, 1996, Journal of Infectious Diseases. This manuscript describes the successful protection of vaccinated chimpanzees from a high-dosage HIV challenge. The chimpanzees, the host animal of HIV, were immunized with a monovalent formulation of AIDSVAX. They were then challenged with a strain of HIV that was 18% at variance in amino acid sequence from the vaccine. This substantial variation was designed to mimic viral variation expected in real-world settings. The dose given to these animals produced infection in all control animals. All of the vaccinated animals were protected.

Genetic and Immunologic Characterization of Viruses Infecting MN-rgp 120-Vaccinated Volunteers Berman, et al, 1997, Journal of Infectious Diseases. This study examined HIV infections that occurred in people participating in monovalent vaccine trials. It demonstrated that most infections were due to incomplete immunization, or to infection by viruses that differed from the vaccine immunogen. By examining the viruses that infected people vaccinated with monovalent AIDSVAX B, the study arrived at two conclusions: (1) The vaccine may have protected volunteers against the viral strains that it was designed for. (2) The vaccine could be improved so as to broaden potential protection against additional viral strains. The study provided information regarding how the monovalent MN vaccine could be improved by adding another component (GNE8) to increase the breadth of the antibody response. The resulting bivalent vaccines, AIDSVAX B/B and B/E, are currently being tested in two Phase III clinical trials.

Development of Bivalent rgp120 Vaccines to Prevent HIV Type 1 Infection Berman, 1998, AIDS Research and Human Retroviruses. This is an in-depth description of the logic used to combine primary and T-cell adapted viruses to make the bivalent vaccines used in the U.S. and Thailand. It describes how Phillip Berman, Ph.D., VaxGen’s Senior Vice President of Research and Development and the vaccine’s co-inventor, used the breakthrough information described in the previous article and molecular epidemiologic information to redesign the vaccine to broaden its neutralizing breadth. It reports the first indication that neutralization of primary isolates was possible with such vaccines.

Development of Bivalent (B/E) Vaccines Able to Neutralize CCR5-Dependent Viruses from the United States and Thailand Berman, et al, 1999, Virology. This article describes preclinical animal studies in rabbits and demonstrates that recombinant gp120 can induce neutralization of a broad range of primary isolates. The findings demonstrate for the first time that the magnitude and quality of the immune response to HIV-1 can be improved by combining recombinant gp120s from different genetic subtypes.

AIDSVAX (MN) in Bankgkok Injecting Drug Users: A Report on Safety and Immunogenicity, Including Macrophage-Tropic Virus Neutralization Migasena, et al, 2000. AIDS Research and Human Retroviruses. The study describes the safety and immunogenicity of monovalent AIDSVAX in Thai volunteers circa 1995. Typical of AIDSVAX, 100% of the volunteers develop a long-lasting antibody response. Even though the vaccine was monovalent, some of the vaccinees developed the clear ability to neutralize primary isolates of HIV.

Safety and Immunogenicity Evlatuation of HIV-1 Vaccines AIDSVAX® B/B and AIDSVAX™ B/E — Preliminary Results Judson, et. al.
Initial Report of a Phase I/II Trial of AIDSVAX™ B/E rpg120 HIV Vaccine — Bangkok, Thailand Pitisuttithum et al.

The two studies above were presented at the 13th International AIDS Conference in Durban, South Africa in July 2000 and arrived at the same conclusion: Both of the bivalent vaccine formulations, AIDSVAX B/B and AIDSVAX B/E, appear safe and produce antibodies in 100% of recipients.

Vaccine-Induced Antibodies to the Native, Oligomeric Envelope Glycoproteins of Primary HIV-1 Isolates. Sandra A. Lee, et al, 2001, Vaccine.
This study describes a new assay developed by VaxGen that could be appropriate for use in large-scale clinical trials of HIV vaccines. The assay measures how well antibodies bind to oligomeric gp120, the naturally occurring form of gp120 from HIV. The assay could offer several advantages to currently used assays, including better sensitivity and specificity, and lower cost/higher throughput. Using this assay, researchers determined that bivalent AIDSVAX B/B improved the magnitude and breadth of the antibody response to HIV as compared to a monovalent AIDSVAX B.