IAVI Report Vo. 5, no. 2

PARIS VACCINE MEETING
continued from page 13
major target antigen of the vaccine), the researchers are repeating the work
using a strain with more gp120. The protected animals did not show
sterilizing immunity but initially had viremia, which was then cleared (similar
to measles and polio vaccines).
Stephen Dunham of the University of Glasgow reported on efforts to
develop DNA vaccines against FIV, and to test whether cytokine adjuvants
impact their efficacy. The researchers set out to improve on an earlier DNA
vaccine that protected against the homologous FIV strain but not against more
pathogenic, heterologous strains. This time they used a DNA defective in
integrase (but with an intact reverse transcriptase gene, permitting one round
of replication after vaccination) administered with either IL-12 or IL-18 as an
adjuvant. The trial showed that, although either cytokine could lead to stronger
CTL responses, they did not improve the level or breadth of protection. The
next step is to test their DNA in a prime boost combination.
Ethics of AIDS vaccine trials
This session featured interesting talks from two developing country
researchers involved in conducting or planning HIV vaccine trials in their
respective countries.
Omu Anzala of the University of Nairobi spoke about a Phase I trial of a
DNA/MVA vaccine, based on a Kenyan isolate of HIV subtype A, that is set to
begin later this year. Although it will enroll only about 40 low-risk volunteers,
mostly from the university community, the proposed trial has garnered
tremendous media attention and spurred national discussion. According to
Anzala, the trial has been received very positively, largely because of its genesis:
the Nairobi team has conducted research on exposed, seronegtive sex workers
in this city since 1988, work that formed the basis for developing this
candidate vaccine through a collaboration with researchers from Oxford
University and the University of Manitoba. "It's been very important that this
is a partnership, not just researchers coming to test a finished vaccine,"
Anzala said.
He also described the questions being raised in the country, most of which
revolve around informed consent. While confidentiality is a key principle, there
has also been much discussion of the role of trial participants' family members,
especially spouses and parents of those just over the legal age of consent. Who
is informed about the participation, especially if pre-trial screening shows a
volunteer to be HIV-positive? Other issues under discussion include invasion of
privacy concerns over questions used to assess a person's level of risk
(including number of sex partners) and their other risk-related behaviors, as
well as HIV treatment for participants who become infected while in the trial.
Next, Sricharoen Migasena of the Taksin Hospital in Bangkok spoke about
the ongoing VaxGen trial in Thailand, the only Phase III HIV vaccine trial
launched in the developing world, and described why the country decided to
approve the trial. Because Thailand has conducted many clinical trials in the
past, it has an established system for ethical and scientific review that goes
back more than two decades and encompasses a National Ethics Committee
and many institutional review boards. When the AIDS epidemic took off in the
mid-1980's, Thailand became active in running Phase I and Phase II HIV
vaccine trials (10 so far), in the process establishing additional infrastructure
for laboratory work and prevention counselling. The decision to move ahead
with the VaxGen Phase III trial was based on several considerations, including
scientific merit (could the trial yield valuable information?), a risk-benefit
analysis and the available infrastructure. Participants who became infected
during the trial will receive treatment according to the national standard,
which at present is two drugs (AZT and ddl or 3TC). Migasena said that the

decision not to offer triple therapy (unless this becomes the national practice)
was made out of concern that a higher standard of treatment would constitute a
form of inducement for (high-risk) people to participate in the trial. *

David Gold
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The IAVI Report is published bi-monthly by the
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Copyright ~ 2000. All rights reserved.
IAVI is a scientific organization founded in
1996 whose mission is to ensure the development of safe, effective, accessible, preventive
HIV vaccines for use throughout the world.
Lean in structure and catalytic in nature, IAVI
focuses on three key areas: accelerating scientific progress; education and advocacy and
creating a more supportive environment for
industrial involvement in HIV vaccine development.
IAVI is a UNAIDS Collaborating Centre. Its
supporters include the Rockefeller, Alfred P.
Sloan, Starr, William H. Gates, Until There's A
Cure and Vincent P. Belotstky, Jr. Foundations,
as well as the U.K. and Dutch Governments,
the World Bank, UNAIDS, the National AIDS
Trust and Fondation Marcel Mrieux. IAVI
also receives support from Crusaid, the Elton
John AIDS Foundation, Levi Strauss International, Angel Music, Ltd., Glaxo Wellcome

and generous individuals around the world.

J