NIAID Collaborates with VaxGen on Vaccine Studies

National Institute of Allergy and, Infectious DiseasesFOR RELEASE, Tuesday, August 18, 1998Q & A on NIAID/VaxGen Collaboration, Patricia Randall, [email protected]

As part of its broad-based HIV/AIDS vaccine research efforts, the National Institute of Allergy and Infectious Diseases (NIAID) will collaborate with VaxGen, Inc., in research projects to be done in conjunction with the company's current Phase III AIDS vaccine studies.

The collaboration will entail research - in addition to that currently called for in VaxGen's trial plans - on immune responses induced by AIDSVAX, as well as use of AIDSVAX in combination with other vaccines currently being studied by NIAID. Additional joint research aimed toward creating formulations of AIDSVAX for viruses prevalent in developing nations is also under discussion.

"The effort to develop a safe and effective vaccine against HIV/AIDS is a global imperative and the highest priority of the NIH AIDS research program," says Anthony S. Fauci, M.D., NIAID director. "We expect this collaboration with Vaxgen to take us closer to our mutual goal."

In June, VaxGen began its trial of AIDSVAX. AIDSVAX has been shown to be safe and to stimulate antibody production. The three-year study is the first large-scale trial of an HIV preventive vaccine and will involve 5,000 volunteers at about 40 clinical sites in North America. VaxGen is sponsoring these trials and anticipates conducting additional Phase III studies in Thailand.

NIAID is also studying other vaccine designs aimed at stimulating different components of the immune system. These activities are part of NIAID's ongoing efforts to determine systematically the effects of immunization and the potential for different approaches to prevent HIV disease.

VaxGen, Inc., based in South San Francisco, Calif., is a biotechnology company committed to making an HIV vaccine for worldwide use.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the Internet via the NIAID web site at http://www.niaid.nih.gov. August 18, 1998

Questions and Answers on NIAID/VaxGen Collaboration

Q: What is the NIAID/VaxGen collaboration?

A: The collaboration involves the Phase III trial of the AIDSVAX vaccine, which began in June 1998 and is being conducted by VaxGen. This trial, with 5,000 volunteers, has been designed to determine the ability of AIDSVAX to prevent HIV infection or modify the course of HIV disease.

NIAID will collaborate with VaxGen by expanding the scientific range of the Phase III study and by providing expertise in certain areas of immunology. As the Phase III trial proceeds, NIAID will sponsor the collection of samples from study volunteers, with the subsequent goal of evaluating immune functions in vaccinated volunteers, including infected vaccinees.

These evaluations will enable VaxGen and NIAID to determine the ability of AIDSVAX to induce different components of the immune response. For example, should the vaccine have protective activity, it would then be possible to determine which components of immunity correlated with protection.

Q: Does NIAID have any other ongoing collaborations?

A: Yes, NIAID also is collaborating with a number of other vaccine companies. Since no one can be sure which vaccine is most likely to succeed, it is appropriate and necessary that a number of vaccine designs be explored simultaneously. VaxGen is using a subunit vaccine of the gp120 protein, exploring the role of antibodies in protection. NIAID, in collaboration with other companies, is exploring other strategies, including a combination vaccine that attempts to induce both cytotoxic T cells and antibodies. Together, these studies will systematically determine the effects of immunization and the role of these vaccine approaches in preventing HIV disease. Provided that the clinical trials are performed according to the highest medical standards, both studies will advance HIV vaccine development. Obviously, it is hoped that one or both vaccines will have sufficient potency to be put into general use. Even if they do not, the studies will provide valuable knowledge regarding the next approaches to be considered.

Q: In what stage of development is VaxGen's vaccine?

A: VaxGen's AIDSVAX vaccine is currently in late-stage (Phase III) clinical trials in 5,000 volunteers in North America. The study will last three years.

Q: How has NIH been involved with the VaxGen vaccine?

A: NIH has conducted six Phase I studies and one Phase II study using VaxGen's first- generation AIDSVAX vaccine. Now that the second-generation AIDSVAX vaccine has entered Phase III clinical trials, NIH is collaborating with VaxGen in the evaluation of immunological responses to their vaccine, as described above, as part of the VaxGen Phase III trial.

Many investigators affiliated with the NIH-supported AIDS Vaccine Evaluation Group (AVEG) and HIV Prevention Trials Network (HIVNET) are independently participating in the VaxGen Phase III study. Such independent collaborations are common among NIH-supported clinical investigators; NIH encourages such arrangements with the caveats that NIH funds are spent only on NIH-related activities and that the investigators fulfill their clinical trials obligations to NIH.

Q: Are antibodies, cytotoxic T cells or both needed for an effective vaccine?

A: No one knows for sure what is needed for an effective HIV vaccine. In some vaccines for other diseases, antibodies appear sufficient to prevent infection, while in other vaccines, a combination of different immune responses may be important.

In general, antibody is most effective during the earliest phases of infection, when it binds to virus, neutralizing it and preventing its entry into cells. If viral infection is established, specialized immune cells (called killer T cells) eliminate the virus-infected cells.

AIDSVAX induces an antibody response. Other vaccine concepts are designed to induce both a killer T-cell response and antibody production. Whether one or a combination of both vaccines are required will be determined in the Phase III trials.

Q: While AIDSVAX is the first vaccine in Phase III trials, there has been skepticism about its effectiveness. Why is that?

A: The AIDSVAX vaccine was developed over a period of a decade. The first-generation vaccine (monovalent) was found to be safe and induced an immune response in humans. However, the immune response did not cover all strains of HIV circulating in the population. The second-generation vaccine (bivalent) contains additional gp120 protein and now has a broader representation of HIV strains. Much of the skepticism comes from the earlier studies of the monovalent vaccine, as well as some doubt about the effectiveness of an antibody-only response. However, only a clinical trial will determine the true activity of the second-generation vaccine.

Q: Now that AIDSVAX has entered Phase III trials, does that make you doubt your decision in 1994?

A: No. NIAID and VaxGen have had long, deliberate discussions about events in the HIV vaccine field. The current AIDSVAX product is superior to the first-generation product considered in 1994. VaxGen is pursuing its development, and NIAID is pursuing development of the combination approach. It is in everyone's interest to ensure that all of these studies proceed quickly and according to the highest scientific standards.

Q: How is the current VaxGen vaccine different from the candidate vaccine proposed in 1994?

A: The vaccine in 1994 was monovalent, in that it contained gp120 from the then known dominant strain of HIV. The AIDSVAX of 1998 is bivalent, containing gp120 from strains of HIV known from laboratory and genetic studies to be representative of those seen in people at the onset of HIV infection. AIDSVAX has been shown to be safe and is considered a superior subunit vaccine candidate when compared to earlier versions.

Q: Which of the two vaccines, AIDSVAX or the combination vaccination mentioned above, do you consider superior?

A: We do not know whether or not either is effective, and we cannot know that until the trials are completed.

Q: What does it mean for an AIDS vaccine to work?

A: The ultimate goal of a vaccine is to prevent infection. Short of that, the ability to prevent AIDS or to favorably modify the course of HIV disease would be an important advance.

Prepared by: Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892-2520

U.S. Department of Health and Human Services