Panel to Review GP160 Vaccine Candidate: Report of the Meeting

well-tolerated. Neutralizing antibodies to HIV were produced at
higher titer and in a greater percentage of recipients with the
gpl20 vaccines from Genentech and Biocine than the gpl60 vaccine
from MicroGeneSys.
Another approach has been to use a combination of vaccines
in which one "primed" the immune system with a live-virus
recombinant vaccine and then boosts with a subunit protein like
gpl60. This may be more analogous to a seropositive person who
is "primed" by the virus with which they are infected. In this
experiment, gpl60 was an excellent "booster," although it
produced high titers of neutralizing antibodies for only a short
time and repeated boosting did not increase neutralizing titers.
However, this approach did produce persistent CD8+ cytotoxic
lymphocytes (CTLs) in these volunteers. This combination vaccine
is the only one studied to date that produces CD8+ CTLs to the
HIV envelope.
Dr. Corey then discussed other gpl60 studies in HIV
seropositives, providing additional comments on the clinical
study by Dr. Robert Redfield at WRAIR and his collaborators that
was published recently in the New England Journal of Medicine. As
noted in Dr. Redfield's article, the MicroGeneSys gpl60 vaccine
induces antibody responses in HIV-infected individuals of
interest, Dr. Corey noted that the responses are not consistent
from one individual to the next or even within a single
individual over an extended period. Whether or not this is due
to HLA type or past "priming" from different HIV strains is not
clear.
Dr. Corey then offered an alternative suggestion as a
possible interpretation of the difference in CD4 cell counts
between gpl60 responders versus non-responders. He stated that
response to the vaccine may be "an indicator" of better innate
host resistance, and, as such, responders were more likely to
control their HIV infection than non-responders. Thus, the
vaccine was an "indicator" rather than the cause of better CD4
cell counts over time. Only further studies and use of a
concurrent control population will answer this question.
Dr. Corey then reviewed data from another HIV seropositive
trial that is still in progress. This trial uses the Biocine
non-glycosolated protein env 2-3. While the trial is still
blinded, he presented data to show novel immune responses were
also induced by this vaccine.
Dr. Corey then summarized his thoughts about the HIV
vaccines in seropositive individuals. He stated that it was too
early to tell whether or not these vaccines would have a
significant impact on HIV disease. However, it is already
apparent that the antiviral effect of the vaccines are "less than
any currently licensed antiviral [drug products]," he said. This
is not the same as saying they have no clinical benefit, he
added.
The relatively low potency of gpl60, even compared to other
vaccine candidates, leads to several questions about what kinds
of vaccines should be retained or rejected for further