Vaccine update: More optimism among scientists

By Pat Reber Dec 1, 2006, 17:27 GMT

Washington - In the urgent search for a vaccine against AIDS, the International Aids Vaccine Initiative (IAVI) is a chief promoter and coordinator.

Since 1996, it has raised and invested more than 100 million dollars on research and development of an AIDS vaccine, distributing the money to universities and field programmes and institutes working to prevent spread of the fatal disease.

Until recently, it had little good news to report. Despite dozens of vaccine trials around the world, the trials had produced few promising candidates.

But this year was different, making 2006 a 'vintage year for vaccine development,' said Lawrence Corey of the HIV Vaccine Trials Network in Seattle at the annual AIDS Vaccine Conference in Amsterdam earlier this year.

There was 'a spirit of optimism that has become quite unusual for this field,' wrote IAVI's Kristen Jill Kresge in the organization's periodic newsletter, VAX.

The reason was evidence that several ongoing clinical trials have induced 'promising' levels of something called 'cellular immune responses.' In fact, the response levels are three times greater than just several years ago, according to the newsletters.

The familiar approach to vaccines - using the live virus to induce antibodies but not cause the illness - doesn't work with HIV, and in some cases, has even produced a live virus in the body.

The alternate route of causing a cellular immune response involves programming the body's T-cells to 'search out and kill virus-infected cells,' according to Dr Wayne Koff, a top IAVI official in a recent interview.

Some researchers worry about the effectiveness of such an alternate route, pointing out that licensing has never been granted for a vaccine that only provokes such a response. Government agencies are usually looking for an immunization that induces a antibody response to neutralize a disease.

But the recent strides forward on cellular response have inspired enthusiasm in the vaccine research community - even if it is for a vaccine that may only slow the progression of the disease and lower the transmission likelihood.

In fact, even a '50 per cent effective vaccine given to just one- third of the population' in the developing world could cut the number of new HIV infections by at least half in 15 years, according to IAVI.

According to the newest figures published by UNAIDS and the World Health Organization, another 4.3 million people were infected over the past year, more than half of them in sub-Saharan Africa, bringing the world total to 40 million people living with AIDs.

The disease also killed 2.9 million people - many of them in the prime earning and parenting phases in developing countries, producing devastating economic effects.

Vaccine researchers - along with developers of newly emerging vaginal microbicides that can kill the virus on contact - believe that the only way to stem the epidemic is by prevention.

Yet money for research is in short supply. Researchers estimate that only about 1 per cent of the 70 billion dollars the world spends on research for all medicines every year goes to AIDS vaccine research.

In the desperate race for a solution, the US and other governments are trying to attract private firms like Merck to the unprofitable field with financial offerings - with the requirement that all results are shared.

Still, experts warn it could be another 10 years before a vaccine is on the market.

Experts at the international vaccine conference in September in Amsterdam heard about various encouraging projects. Eric Sandstroem of the Karolinska Institute, Sweden, described a DNA vaccine that produced positive immune responses in 33 of 36 participants, IAVI reported. Larger trials are planned for Tanzania.

The European Vaccine consortium (EuroVacc) recorded a 90 per cent immune response among volunteers in Britain and Switzerland who received a DNA plasmid vaccine, the IAVI report said.

Vaccines must undergo rigorous testing in the laboratory and be proven safe for human beings before the final phase of testing, which measures how effective they are. There are dozens of trials ongoing around the world, increasingly with close collaboration between researchers in the affluent and developing worlds.

In Uganda, for example, researchers at Makerere University in Kampala are testing an AIDS vaccine on 50 infants to prevent transmission of HIV from mother to child during nursing. The vaccine,developed by Sanofi Pasteur, has already been tested on infants in the United States and adult volunteers in Uganda.

Merck's vaccine, now in the last phase of testing on 3,000 volunteers in South America and the Caribbean, is an improvement over the disappointing Vaxgen that came to a dead end in Thailand in 2003, Koff said. Results are not expected until 2007 or 2008.

The Merck vaccine is at the top of the pipeline because of its advanced timeline, Koff said.

Another top candidate comes from the US National Institutes of Health (NIH), HVTN 204, and contains not only a wider variety of DNA from different parts of the virus, but also snippets from the three leading global strains of HIV - the first promising candidate to offer such global potential.

It is being tested on 500 volunteers in North and South America, Africa and the Caribbean, vaccine project director Dr Gary Nabel said.

Vaccine development has been slow for good reason, according to Dr Larry Corey, principal investigator of HIV Vaccine Trials Network (HVTN) based in the state of Washington.

'The virus is a formidable foe with respect to its ability to change its outer coat,' Corey said in an interview with KUOW radio in Seattle.

The wealthy Bill and Melinda Gates foundation is credited with jump-starting AIDS research, pumping 1.1 billion dollars over 10 years into the field.