The Potential Use of HIV Vaccines for the Treatment of HIV Infection: Scientific Summary of the State-of-the-Art

The OAR also sponsors and provides staff support for the AIDS Program Advisory
Committee-Vaccine Subcommittee, which is designed to provide advice and
guidance on cross-NIH AIDS vaccine-related efforts. In addition, the OAR
participates in the PHS AIDS Vaccine Research and Development Subgroup that
provides cross-PHS and cross-federal agency coordination and cooperation in
the development and testing of AIDS vaccines.
III. Current Status of HIV Vaccine Research - Prophylactic HIV Vaccine
Candidates
While some early work in the clinical testing of HIV vaccines has been
completed, a significant amount of testing is currently being conducted by the
NIH, Walter Reed Army Institute of Research (WRAIR) and by individual
pharmaceutical companies. The remainder of this document elaborates the
current status of HIV vaccine clinical research, including:
o vaccine candidates for prevention of HIV infection (prophylactic
vaccines) and
o vaccine candidates for treatment of persons already infected with
HIV (therapeutic vaccines).
The status of research on prophylactic applications will be briefly summarized
prior to more in depth discussion of the status of testing of candidate
vaccines for therapeutic purposes.
The goal of a prophylactic vaccine is to stimulate an immune response in an
uninfected individual that will result in protection from infection or disease
upon subsequent exposure to the virus. There are several obstacles to the
development of an effective prophylactic HIV vaccine. First, the correlate(s)
of protection from HIV infection or progression is not known. However, animal
studies have demonstrated that (1) at least some candidate envelope vaccines
can protect chimpanzees from infection (reviewed, 53), (2) polyclonal or
monoclonal antibody administered passively can protect chimpanzees from HIV
infection, and (3) cells from individuals immunized with a combination of
vaccines (vaccinia-env + gpl60) can protect SCID/hu mice from HIV infection.
Second, the virus can be transmitted either in a free virion form or via
infected cells; vaccines that induce both antibody and cell-mediated immunity
and may be required to block infection by free virions and to eliminate
infected cells from the body. Third, the major form of transmission of HIV is
through sexual contact; an efficacious vaccine may require induction of HIV-1
specific mucosal immune responses. Fourth, the unprecedented degree of
genetic variation of HIV found worldwide and even within a given geographic
area suggests that broadly cross-reactive immune responses will be needed to
protect an individual from all subtypes of virus to which the individual might
be exposed. Finally, because certain epitopes on HIV proteins may mimic host
proteins, there is a theoretical possibility that immune responses to vaccines
might result in auto-antibodies that could trigger autoimmune disease.