Good and Bad News from AIDS Vaccine Tests

By Thumbi Ndung'u

Most public health experts agree that a safe, effective and affordable vaccine would be the most potent weapon against this modern day plague.

In the 1980s and early 1990s, after HIV was identified as the cause of Aids, scientists believed that a vaccine against the virus would soon be developed. The optimism was born of the fact that modern science had been successfully employed to produce effective vaccines against such deadly scourges as polio, smallpox and hepatitis B.

In fact, in the 1980s, many thought the virus would be no match for the new techniques being developed in many of molecular biology laboratories. It turned out, however, that the virus was much smarter than originally conceived.

It rapidly became clear that no two HIV viruses were identical, even when they were obtained from the same individual. HIV viruses exist in an infected person as different but related viruses, much like cousins living in the same village.

This is one reason why it is so difficult to develop a vaccine. At any one time, the body is fighting against millions of different but related viruses, known scientifically as quasi-species. This problem is further complicated by the observation that HIV viruses differ from one region of the world to another and up to 10 different HIV sub-types have been reported.

For example, the Oxford/Nairobi vaccine currently undergoing clinical trials is based on HIV-1 subtype A, because this is the most common sub-type in Kenya.

Most traditional viral vaccines were made from weakened (or so called attenuated) or killed viruses. These vaccines were thought to be successful because they targeted cells of the immune system in the body to produce chemicals known as antibodies.

Antibodies are chemicals that attach to "foreigners" in the body, such as viruses and kill or inactivate them. Most vaccines act by mimicking foreign particles, thus activating or training the cells that produce antibodies (B cells) to recognise the "foreigners".

When the real dangerous foreigner (such as a smallpox virus) then comes to infect the body, the B cells spring into action, producing massive amounts of antibodies that kill the foreigner before it can establish himself. This vaccination strategy cannot work against HIV because there are concerns that a weakened HIV can turn into a more dangerous form once inside a vaccine recipient. Furthermore, HIV coats itself with sugar molecules so that antibodies produced by the body cannot bind effectively and kill it.

In addition to B cells, the body has other cells that attack germs known as T cells. T cells work by producing chemicals that help B cells (T helper cells) or can directly kill virus-infected cells (killer T cells). Once HIV infects a cell in the body, some viral proteins made inside the cells are transported to the surface. T cells recognise these foreign proteins and kill the infected cell and hence they are called killer T cells. However, because some viruses hide inside the cell and do not surface, most experts believe that T cells alone cannot eliminate HIV completely from the body.

The Oxford/Nairobi vaccine is based on this concept and aims to make vaccinated people produce killer T cells. Importantly, this vaccine is made from a piece of HIV, not the whole virus, and therefore cannot cause disease.

A number of recent studies in monkeys suggest that the T cell targeted vaccines are likely to reduce the amount of circulating virus in a vaccinated individual but may not completely prevent infection. This is, in fact, what most vaccines do – they don’t completely prevent an individual from infection but they suppress the disease causing agent.

In a study reported in a recent issue of the journal Nature, eight monkeys were given a vaccine that induces the production of killer T cells. All monkeys were then injected with a laboratory generated HIV-like virus that rapidly kills monkeys. All monkeys receiving the vaccine (as opposed to placebo or dummy) became infected but did not develop disease or die. Those who did not receive the vaccine died.

Perhaps the most important lesson from the latest vaccine research is that we need to develop ways of harnessing all available arms of the immune system in order to overcome HIV. The good news is that there are experimental vaccines showing some promise, the bad news is that those vaccines may not be good enough.

* The writer is a Research Associate and Prince of Wales Fellow at HAI, Harvard University, USA.