AIDS: Science at a Crossroads

5. VACCINES: WHERE ARE WE NOW?
HIV - a challenge to vaccine designers
The search for a vaccine or vaccines against HIV has proved much more difficult than expected.
Vaccines aim to protect people from infection with a particular microbe by stimulating their immune
system to make a protective response against it. They do so by presenting the immune system with a
"dummy" microbe - either a killed one, or a part of one, or a live but weakened one. But with HIV,
there are some fundamental problems.
* First, the virus is highly variable, not just between the different subtypes (see page 3) but also
within subtypes and even within infected individuals, each of whom may harbour a "swarm" of
diverging variants. A vaccine based on one subtype may or may not provoke an immune response
that "recognises" different ones.
* Equally difficult for the vaccine designer, HIV can enter the body hidden inside an infected cell.
This puts it effectively out of reach of the immune system. No one knows for sure whether the
specific immune response raised by cells in the mucous membranes in sexual organs is crucial for
protection, but the question is an important one because most people become infected through the
mucous membranes of the genital tract during sexual intercourse, not through the bloodstream
during blood transfusion or injection with an infected needle.
* The immune response to infection consists of two broad arms: antibodies, which attach themselves
to the virus and block it out of cells; and T cells, which kill infected cells. Most scientists believe
that both arms of the system will be needed to protect against HIV. But so far, despite intensive
effort, no researchers have been able to pinpoint exactly which parts of the immune response to
HIV matter in protecting people from infection. Until they do, some scientists argue, it will be
difficult to design a vaccine that works. Others, such as Ronald Desrosiers of Harvard University,
disagree: they argue that the history of vaccines has been built on testing vaccines that may not be
understood at all, but which have been found through empirical research to work (8).
* Another problem is the lack of a good "animal model". Scientists usually study an infection and the
effect of an experimental vaccine in animals, such as mice and monkeys, that can be infected and
develop similar or comparable symptoms to humans. The animal can be vaccinated and deliberately
exposed to infection to find out whether the vaccine works. In the case of HIV, however, the best
model is the macaque, infected with the simian immunodeficiency virus (SIV). Chimpanzees can
be infected with HIV-1, but because they are an intelligent, endangered and protected species, in
short supply and prohibitively expensive, scientists are reluctant to use them.
Who will foot the bill?
And, as if the scientific difficulties were not great enough there is another, equally pressing
economic problem. In the 1980s, pharmaceutical and biotechnology companies were enthusiastic
about developing HIV vaccines. Even so, estimates in a report by the Rockefeller Foundation (3)
suggest that the total private sector expenditure on HIV vaccine research in 1993 was around US$
25 million. The public sector, overwhelmingly the US government, spent US$ 135 million. Now
that it is clear that the vast majority of infections are in the developing world, where few people
or governments can afford to buy vaccines at market price, the motivation for the private sector
is reduced - particularly since the US announced that it had postponed any large-scale domestic
field trials of HIV vaccines.
Vaccine trials also pose a number of essential ethical questions. For instance, according to ethical
guidelines on vaccine testing, participants to a trial must be volunteers; they must also be able to
understand the nature of the research involved and any possible risks and effects associated with it.

Because many of the issues linked to HIV vaccines are very complex, this is difficult to establish. For
ethical reasons, people who participate in vaccine trials must also be counselled on how to avoid
infection and to protect themselves. This may in turn reduce the number of people who become
infected, and make it more difficult for researchers to judge how well the vaccine works, but it would

Panos Briefing: AIDS: SCIENCE AT A CROSSROADS 10