In an effort to accelerate vaccine development, the New York−based
International AIDS Vaccine Initiative (IAVI) has awarded the two largest AIDS
research grants ever given by a non−governmental organization. The three−year
grants, worth approximately $4.5 million each, are intended to support two
separate vaccine development approaches through to Phase I clinical trials.
While agreeing that the grants are an important boost, experts caution that
substantial obstacles to HIV vaccine development remain.
IAVI billed the scientific partnerships as "pursuing some of the most exciting
new vaccine technologies in the world." In one project, researchers at the
Universities of Oxford and Nairobi are developing an approach that combines
DNA vaccination with a recombinant vaccinia virus. The other effort, involving
the North Carolina biotechnology company AlphaVax and the University of Capetown,
uses an attenuated, recombinant version of Venezuelan equine encephalitis
virus, which has been shown to induce a T cell−mediated response to
a variety of antigens.
In exchange for research funding, IAVI reserves the option to enter into
one of three intellectual property agreements with researchers: a non−exclusive,
royalty−free license to produce a vaccine for developing countries,
an exclusive license with some restrictions, or receiving 25 percent of the
net royalties from any patents. According to IAVI President Seth Berkeley,
such arrangements will allow a company to recover vaccine costs through sales
in the developed world and ensure reasonable access for developing countries
by preventing the patent holder from pricing the vaccine out of reach for
such nations.
Africa is the epicenter of the worldwide AIDS pandemic and both teams plan
to focus on viral strains prevalent in South Africa and Kenya, where the vaccines
will be tested. But the feasibility of any vaccine is still an open question.
"We're very much aware of instances where the virus evades a response. The
main thing is we don't know whether this will work at all yet," says Andrew
McMichael, who leads the Oxford team. Robert Johnston, professor of microbiology
at the University of North Carolina, Chapel Hill and leader of the AlphaVax
effort, agrees: "[Based on preliminary results], I think we have a reasonable
chance of success in humans. However, I would hasten to add that there is
absolutely no way to accurately predict the outcome at this juncture."
David Baltimore, president of Caltech and head of an NIH committee studying
HIV vaccines thinks that any vaccine "that significantly lowered the plateau
level of virus," would be useful. Dennis Burton, a researcher at the Scripps
Research Institute, California, agrees, but cautions that vaccines with very
low efficacy could be dangerous. "Once you have a vaccine and you talk about
protection, there's a good chance that people will change their behavior,
and if you have these small incremental advances in reductions in transmission
rate, that could easily be offset by behavioral changes," says Burton.
Seth Berkley
Even if such technical and monetary hurdles are overcome, a vaccine might
be blocked politically. In a statement released on World AIDS Day, M. Douglas
Winship, Senior Vice President for Regulatory Affairs at Cel−Sci in
Virginia, says that "while it is generally thought in the Western world that
any vaccine candidate shown to be safe and promising in human studies would
be welcomed by the leaders of the developing world, our experience and that
of others indicate otherwise." According to Winship, a Phase II trial of Cel−Sci's
synthetic peptide vaccine was approved unanimously by Zambia's national AIDS
testing committee, only to be derailed when government officials insisted
that the company also build a laboratory in the country.
Though Berkeley acknowledges that the technical, regulatory and logistical
problems are real, he concludes, "with $20 billion being spent a year on AIDS
[treatment], to not have a serious vaccine effort seems almost criminal."
McMichael supports this view: "The alternative—that the rich countries
should pay for [antiviral] drug treatment [in lesser−developed countries]—is
just so expensive that it makes this option look really quite cheap."
Finally, such private initiatives also force attention on government−funded
efforts to develop a vaccine, namely those of the National Institutes of Health
(NIH). On World AIDS Day—only days after the IAVI announcement—President
Clinton announced that he will increase the NIH AIDS vaccine research budget
by 33 percent to $200 million. However, a director for the office of AIDS
vaccine research established 18 months ago has still not been appointed. Thomas
Lehner, an HIV researcher at St. Thomas' Hospital Medical & Dental School,
London, dismisses the notion that NIH is taking a back seat to nonprofit efforts:
"NIH has really been, in my view, at the forefront of vaccine development
... it would be unfair to the NIH to say that the lead has been taken by IAVI."
