InterPress News Service (IPS) - Sunday, October 4, 1998
Judith Perera

It is seen as particularly important for the developing world, where recent advances in the treatment of HIV/AIDS will have little impact. The high cost of developing and producing new drugs and the lack of available funds for health care in many countries make it unlikely that new therapies will be widely available in the developing world.

"AIDS is a global epidemic, which is especially acute in the developing countries in Africa and Asia," says Dr Prem Sarin, who is responsible for developing a vaccine as scientific head of the Vienna-based company, CEL-SCI.

"By the year 2000, there will be approximately 40 million HIV- infected people world-wide. Without a vaccine there will be no end to this epidemic and whole generations of young adults will be wiped out."

Vaccine development for AIDS is fraught with difficulties - both political and scientific. The identification of the HIV virus in 1984 raised hopes of finding a vaccine, but after 14 years none have come near development, because the main focus has been on finding a treatment for the already infected.

Last year, U.S. President Bill Clinton gave a boost to vaccine researchers by setting a target to identify a vaccine within 10 years and, since then, efforts have been stepped up. The scientific challenges, however, remain huge. HIV is unlike any other virus. Unusually, while people usually produce strong immune responses to the HIV virus they still become ill, adding to the mystery as to how it 'works'.

Scientists do not know which kind of vaccine they should develop - one that produces antibodies that destroy free viruses roaming in the blood - or one that creates white blood cells (cytotoxic lymphocytes) that target and destroy already-infected cells.

A combined approach is possible, by creating a vaccine that stimulates both antibodies and cells. Special study is also being made of less well understood immune responses in the body's mucous membranes in the vagina and rectum, which are ports of entry for sexually-transmitted HIV, and the gut, where experts think the HIV virus may locate itself soon after infection.

Another problem is the lack of suitable animals for testing vaccines, as no animal immune system reacts to HIV the same way as humans. And the HIV virus comes in many different sub-types and appears to mutate and change rapidly. Most interest has focused on so-called 'sub-unit' vaccines, produced by genetic engineering, that targets the glycoprotein coating around the HIV virus. Two types of subunit vaccines have been tested in clinical studies.

The U.S. National Institutes of Health refused early tests by Chiron Corp. and Genentech, Inc (VaxGen). Controversially the firms are now seeking a test in Thailand.

Another approach involves 'recombinant vector' vaccines, which aim to trigger HIV immunity by introducing into the body HIV virus genes carried in engineered bacteria. One vaccine under trial, the 'ALVAC' class, involves the canarypox virus, re-engineered to carry HIV virus genetic material. Produced by the French pharmaceutical company Pasteur-Merieux-Connaught (PMC).

So-called 'DNA vaccines' are also a possibility. These involved injecting selected HIV genes directly into the body. These enable the individual's own cells to make HIV-based proteins which, in turn, trigger natural immune defences in the human blood stream.

Early tests on animals, allowing for the problems of such studies, show promise. They can also be produced relatively cheaply. Companies working on this approach include Merck, PMC, and Chiron, and smaller biotechnology companies such as Apollon and Auragen. Of these, only Apollon has begun human studies.

So-called 'whole-killed' vaccines are another subject of study. These are produced by neutralising the HIV virus by using chemicals, heat or irradiation, allowing them to be injected into the body without lethal effect -- but also allowing the body to develop an immunity.

A similar but more controversial technique involves so-called 'live-attenuated' vaccines -- using live but weakened HIV viruses -- has been considered, but the risk of infecting the uninfected with the vaccine itself is high.

Virus-like particle vaccines (also known as VIPs) are also being researched. They consist of non-infectious HIV 'look-alike' particles that contain one or more, but not all, HIV proteins -- but once again triggering a normal immunity in humans. Similarly there are the 'synthetic peptide vaccines' -- artificial synthesised pieces of HIV proteins similar to the proteins that coat the HIV virus.

Many researchers, however, accept that none of the present vaccine candidates are good enough. Nobel laureate Dr David Baltimore, who chairs the U.S. National Institutes of Health's new AIDS Vaccine Research Committee, doubts that any are worth large- scale tests. He advocates more basic research and small trials which will also attract drug and biotech companies.

"We need to face industry with real opportunities. Right now the pipeline isn't exciting enough -- we're testing concepts that are clearly outdated. Drug companies have made the reasonable judgement that the time isn't right."

Not so CEL-SCI, which is developing a different type of synthetic peptide vaccine. "My main reason for taking up this task at CEL- SCI was the opportunity to move the research and development of a vaccine at a much faster rate than is possible at academic or government institutions," says Sarin.

CEL-SCI's vaccine, now on the second level of three-tier safety trials, is based on peptides found not on the surface of the virus but in the core. These are fairly similar whatever the virus subtype.

"Our vaccine is designed to work against major HIV subtypes (A, B, C, D & E) found in Africa, Asia, North and South America and Europe. In contrast, the envelope-based vaccines being tested are based on the B subtype prevalent in North America and Europe and hence, may not be very useful in the developing countries," Sarin explains.

He adds optimistically: "We believe the prospects are good. We are excited to be developing a vaccine that may save millions of people world-wide, who are at risk of becoming HIV-infected." (END/IPS/jmp/rj/98)
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