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

vaccine candidates. If any product is found to be clearly inferior, it will
be dropped from further study by the ACTG. The trial is scheduled to open in
early 1993. Initial data will be available by mid to late 1993.
The Division of Intramural Research Program of NIAID has sponsored a Phase I
study. The MGS gpl60 (LAI) vaccine was administered to 10 seropositive
patients with CD4+ T-cells >500/mm3. Five patients received 160 ug and the
other 5 patients received 1280 ug. Nine 9 males and 1 female enrolled. The
study demonstrated safety of the product and development of cellular immune
responses to the vaccine (lymphocyte proliferation) in 7/10 vaccine
recipients. There was no significant effect on CD4 count noted over a 14
month period. No viral burden data are available (52).
Future ACTG Trial: Tl-SP1--[A]. This synthetic peptide, adjuvanted in
Incomplete Freund's Adjuvant (IFA), contains several immunodominant peptides
for LAI, MN and SF-2 strains of HIV, as well as an HLA-recognition peptide.
Preclinical studies are currently in progress. Phase I trials are anticipated
to begin in mid-1993.
Future ACTG Trial: British Biotech VLP-p24. This p24 core-based peptide is
expressed by recombinant yeast as a viral-like particle and adjuvanted in
alum. Phase I studies will begin in early 1993.
Phase I: Non-NIH Sponsored Therapeutic Vaccine Candidate Trials
The following therapeutic vaccine candidates are being evaluated in non-NIH
sponsored Phase I trials (TABLE 11):
1. MGS gpl60 (LAI):
a) WRAIR/DoD has completed a 30 patient non-randomized, no placebo trial
in seropositive patients with CD4 cells >400/mm3, who are not receiving
antiretroviral therapy. The study demonstrated the safety of this
product and development of novel and expanded cellular and humoral
immune responses. Specifically, the end-points studied in terms of
immunogenicity were antibodies directed against gpl60, p66, and p24 as
well as antibodies to whole viral lysates of HIV strain MN, and
neutralizing antibodies against 3 HIV strains (IIIB, RF & MN). HIV
cellular immunity was measured by the use of lymphocyte proliferation
assays against gpl60, p24 and a baculovirus expressed control protein.
Vaccine responsiveness was defined as a reproducible increase in
cellular and humoral responses; only HIV-envelope specific responses
that were temporally associated with the vaccinations were scored. A
patient who only mounted one of the two classes of response (cellular or
humoral), they were classified as non-responders.
In the initial 240 day trial, the product was demonstrated to be safe.
19/30 patients were found to be immunologic responders. Neutralizing
antibody against either IIIB, MN or RF was found in 7 patients. The
mean lymphocyte stimulation index (LSI) to gpl60 among those patients