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

29). The longest period of volunteer followup of an envelope product capable
of binding CD4 is now about two years after immunization of seropositive
individuals and over 20 months in seronegative individuals.
With respect to immunogenicity, almost all products evaluated to date induce
binding antibody which lasts weeks to months, and almost all induce some level
of functional antibody, usually against homologous strains of virus (TABLE 6)
(reviewed, 50). With respect to cell-mediated immunity, lymphoproliferative
responses to candidate vaccines have been found in every trial to date where
data are available (TABLE 7) (reviewed, 50). To date, one NIH-sponsored
protocol in which volunteers were administered vaccinia expressing gpl60
(HIVAC-le) followed by boosts with gpl60 (VaxSyn) resulted in induction of
CD8+ cytotoxic T lymphocytes (CTLs). Adoptive transfer of Peripheral Blood
Mononuclear Cells (PBMC) from volunteers with CD8+ CTL to SCID mice have shown
that these cells are functional (J. McElrath, L. Corey, personal
communication). Picard and co-workers reported generation of CD8+ CTL by
immunization with vaccinia-gpl60 and/or subunit immunogens (5, 10).
The NIAID Prophylactic HIV Vaccine Research and Development Agenda
The NIAID's Division of AIDS (DAIDS) has developed a prophylactic HIV vaccine
research and development agenda outlining the most critical questions facing
HIV vaccine development at this moment, the status of current research,
information gaps that presently exist, and NIAID resources that are directed
toward addressing the critical questions. This agenda is under review and
will be released by the NIAID in December, 1992. A brief synopsis of the
NIAID vaccine agenda is provided here and a draft copy of the plan is attached
(Included in Briefing Book).
In order to accomplish the goal of developing a vaccine or vaccines that will
prevent HIV infection and/or disease and that will prevent the transmission of
HIV from mother to fetus/newborn, NIAID has established two broad objectives:
1. Promote the development of HIV vaccine(s) through preclinical and
clinical research in direct support of licensure.
2. Foster basic research that will lead to candidate vaccines with
improved efficacy.
The NIAID will continue a systematic immunological evaluation of all promising
vaccine candidates in Phase I and Phase II trials to determine if there are
differences in safety and immunogenicity in different populations including
those at higher risk for exposure to HIV, and to determine which immunological
response(s) are required to provide protection. Standardized methodology for
the measurement of immune responses, including CTLs and mucosal immune
responses, will continue to be developed and implemented to ensure that
complete immunologic evaluation is accomplished.