August 18, 1998
Questions and Answers on NIAID/VaxGen Collaboration
What is the NIAID/VaxGen collaboration?
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
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
Does NIAID have any other ongoing collaborations?
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
In what stage of development is VaxGen's vaccine?
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
How has NIH been involved with the VaxGen vaccine?
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.
Are antibodies, cytotoxic T cells or both needed for an effective
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.
While AIDSVAX is the first vaccine in Phase III trials, there has been
skepticism about its effectiveness. Why is that?
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
Now that AIDSVAX has entered Phase III trials, does that make you doubt
your decision in 1994?
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
How is the current VaxGen vaccine different from the candidate vaccine
proposed in 1994?
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.
Which of the two vaccines, AIDSVAX or the combination vaccination
mentioned above, do you consider superior?
We do not know whether or not either is effective, and we cannot know
that until the trials are completed.
What does it mean for an AIDS vaccine to work?
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.
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