Panel to Review GP160 Vaccine Candidate: Report of the Meeting

HIV vaccine candidates in clinical trials: preliminary
findings and analyses. For the two products in Phase I trials
for which data have been reported, each has produced novel
humoral immune responses. They also generate lymphoproliferative
responses to HIV antigens, and one of the vaccine candidates
appears to increase cytotoxic T cells. Preliminary findings from
several clinical studies of candidate vaccines, including gpl60,
suggest that CD4 levels may stabilize in individuals receiving
the vaccine, although no conclusions can be drawn due to the
small size and generally uncontrolled design of these studies.
There is "no reproducible evidence" of a positive effect on
viral load, according to Dr. Hoth and other meeting participants.
Importantly, there is no obvious worsening of the overall immune
status of the treated population, even if there is no clear
clinical benefit for HIV-infected individuals whose T cells are
still at relatively normal levels.
Dr. Valentine provided additional details from an AIDS
Clinical Trials Group (ACTG) clinical trial testing the
MicroGeneSys gpl60 vaccine in HIV-infected, asymptomatic
individuals. The in vitro proliferative responses of lymphocytes
from gpl60 vaccine recipients to the immunogen, and in some
patients to envelope proteins from a different isolate made in
different expression systems, were "vigorous and astounding," he
said, and in some patients quite broad, including proliferative
responses to HIV antigens not in the vaccine. Moreover, these
responses are not seen in HIV-infected individuals in a control
group who were exposed to a hepatitis vaccine instead of to
different doses of gpl60. Vaccine responses included production
of new antibodies to conserved determinants of the envelope
protein and elevation od CD4 and CD8 cytotoxic lymphocytes.
There was a modest difference in the rate of decline of CD4
counts in favor of the HIV vaccine-treated group, but the
difference was not statistically significant.
Therefore, a summary of the information known to date about
therapeutic HIV vaccines concludes that these vaccines: 1) are
safe, at least in short-term studies; 2) show no evidence of
enhancement of infection; 3) produce new immune responses; 4)
have no definite effect on viral load; and, 5) have shown, in
some trials, unconfirmed evidence of a flattening of the slope of
the CD4 counts.
Dr. Lawrence Corey of the University of Washington in
Seattle also presented findings from on-going studies of several
gpl60 vaccines that are being tested in HIV-infected and
uninfected individuals.
Dr. Corey first reviewed the results of the Phase I trials
of HIV envelope vaccines that had been conducted within the
NIAID-supported AIDS Vaccine Evaluation Units (AVEUs). While the
results of these studies may not be applicable in all aspects to
seropositives, they do allow one to compare the relative ability
of each vaccine to induce antibodies to HIV as all sera were
evaluated in a central laboratory supported by NIAID, at Duke
University. All the HIV envelope vaccines tested were safe and

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