[Letter to Daniel K. Inouye from Anthony S. Fauci]

Animal models have played a critical role in the development of several vaccines. Most
recently, studies with HIV vaccine candidates in chimpanzees were crucial to the development
of successful hepatitis B vaccines. Although there is not an ideal animal model for HIV
infection and AIDS, the scientific community is in general agreement that HIV infection in
chimpanzees and SIV infection in rhesus monkeys provide valuable models to evaluate
candidate vaccines. HIV can infect chimpanzees in an experimentally reproducible manner,
and thus provides a model for HIV infection; the limitations of the chimpanzee model include
the small numbers of available chimpanzees for study and the lack of disease associated with
HIV infection. SIV is a very close relative of HIV, and reproducibly infects several species
of monkeys, causing an AIDS-like disease quite similar to HIV disease in humans. Under
experimental conditions, greater than 80% of SIV-infected monkeys will succumb to SIV
infection and eventually die within a period of 1-2 years of opportunistic infections. The
limitations of the SIV model stem from subtle differences between SIV and HIV.
The NIAID recognizes that it would be inappropriate to select a candidate vaccine for efficacy
trials solely on the basis of animal model efficacy data. Recognizing the limitations of these
animal models, scientists continue to cross-walk information gained from preliminary human
trials with data obtained from these animal models, in efforts to define Ehe best candidate
vaccines for efficacy testing. Currently, the animal models are providing information on
which candidate vaccines protect against infection and disease. They also hold the promise of
providing important information as to which immune responses must be stimulated to elicit
protective immunity against HIV and related retroviruses. This information will be useful in
helping to predict the effectiveness and longevity of the human immune response to HIV
vaccines in efficacy trials.
8. Would we learn more about the efficacy of AIDS vaccines in humans by testing available
vaccines for efficacy in humans, outside of the U.S. Wfnecessary, than by limiting efficacy
testing of vaccine candidates to chimpanzees or other primates?
Evaluation of candidate HIV vaccines is currently not limited to chimpanzee and primate
testing. More than 10 products are being evaluated in clinical trials worldwide, and it is
anticipated that several others will be entering clinical trials in the near future. These trials,
in addition to providing critical safety data for these candidates, are also providing
comparative immunologic data on the relative strengths of candidate vaccines in eliciting those
immune responses which most likely are instrumental in providing protection against HIV.
Information obtained from human clinical trials of vaccine candidates is the principal
determinant for progression of vaccines into larger studies, with animal efficacy data
providing important supplemental support. We are committed to insuring that the best of
these candidates progress rapidly into efficacy trials, and have initiated programs to establish
infrastructure support for efficacy trials outside of the U.S., to complement the domestic
vaccine efficacy trials effort.