AIDS: Science at a Crossroads

be unethical not to counsel people in this way, Another problem is that participating in a vaccine trial
might make people feel that they are protected - and encourage them to practise behaviour which
increases their HIV risk.
Nevertheless, concerned scientists in both the public and private sectors are now working to establish
a new global initiative to accelerate the development of vaccines that the world can afford. The
Rockefeller Foundation report suggests that the initiative would require collaboration between the
public and private sectors and could be modelled on a number of different existing mechanisms such
as the International Task Force on Hepatitis B Immunization or the Children's Vaccine Initiative. It
should also focus on developing vaccines based on subtypes of the virus that are found worldwide, such
as A, E, C and D, and not on subtype B, which has dominated the epidemic in the US but which will
become increasingly less important in the global picture.
How researchers are tackling the issue
So far, more than a dozen candidate vaccines have been tested in small groups of people, mainly in the
US and Europe, to establish whether they are safe and to find out what sort of immune response they
provoke - two essential steps which have to be completed before a vaccine can be tested for its
capacity to prevent infection. Most of these vaccines are based on genetically engineered forms of
HIV's protein coat gpl20. All but one have been based exclusively on subtype B.
Two vaccines made by US companies have been tested in large-scale safety trials. So far, however,
there have been no trials to test whether the vaccine can actually protect people from infection, but
trials are due to begin next year on these vaccines. To establish whether a vaccine can protect people
from infection, researchers will have to vaccinate a large number of people at high risk of infection,
half with vaccine and half with a "dummy" vaccine or placebo, and then compare the numbers that
become infected in each group. If the group that received the real vaccine has significantly fewer
infections than the placebo group, the vaccine will be judged to have given some protection.
In the meantime, the effects of these vaccines have been measured in laboratory studies where blood
samples from vaccinated people are mixed with virus to see whether the vaccine stimulates antibodies
and T cells and whether these can combat the virus. Overall, most of these vaccines stimulate
antibodies against the virus and a few stimulate T cells, but in no case does the response last for long
or at any great strength. It is not clear how much protection these vaccines would offer.
An important development in the 1990s has been the discovery by Dr Ronald Desrosiers, at Harvard
University, of a very different approach based on a live, but genetically altered virus. Desrosiers found
that a vaccine based on a live form of SIV can protect macaques from infection with the wild virus.
The altered form of SIV used in the vaccine had had certain pieces of genetic material removed and
failed to cause disease in the monkeys.
However, there are major safety concerns. No one knows whether a live but weakened and "disarmed"
virus could regain its strength and its weaponry, through gene mutation or through recombining with
the natural virus. Other researchers have found that deleted pieces of genetic material in SIV can
"rebuild" themselves, raising the possibility, however remote, that the vaccine virus could revert to
normal and cause disease. Elsewhere, researchers discovered that infant macaques born to the
vaccinated animals developed disease.
Taken together, these concerns are likely to make authorities such as the US Food and Drug
Administration highly nervous of even considering authorising tests in people. Nevertheless, scientists
argue that where the risk of HIV infection is very high, the relative risk of complications from the
vaccine may be a risk worth taking. Following a meeting at WHO in Geneva in October 1994, Dr
Edward Mbidde, head of Uganda's National AIDS Committee, said the Western nations "had not seen
the epidemic" and that its pace and scale in his country demanded action.

A WHO expert committee argued in June 1993 that a highly effective vaccine with a risk of serious
adverse reaction of 1 in 100,000 might be preferable to the risk of infection in some communities, or
preferable to the risk that a less effective vaccine might fail. In some populations, such as users of

11 - Panos Briefing: AIDS: SCIENCE AT A CROSSROADS