HIV vaccine research landscape 'not all doom and gloom'

New approaches mean there is still hope for an effective HIV vaccine, Australian researchers have said in the wake of today's release of disappointing AIDS vaccine results by US company VaxGen.

Dr Sean Emery, head of therapeutic and vaccine research at the National Centre for HIV Epidemiology and Clinical Research at the University of NSW, said, "It does not work.

"But that's the result most expert commentators expected. It would be a travesty if the result led everyone to feel that it's all doom and gloom in the HIV vaccine field."

Emery said that even when the trial began in 1998, the VaxGen vaccine represented "old technology", and research had moved on.

Conventional vaccines that induced only the antibody arm of the immune response were always likely to fail, because they were ineffective in destroying HIV-infected cells. "VaxGen took an essentially empirical approach, extending the success of vaccines for other common diseases to HIV," he said.

"There was a substantial move away from the conventional vaccine approach in the late 1980s and early 1990s, but VaxGen continued its development program through to yesterday's announcement, and to its notional endpoint at the end of the year, when the results of the Thailand study become available."

Emery said that since most investigators in the field decided empiricism was not the way to go, the focus of vaccine development had been on inducing the cytotoxic T-mediated response.

"It has been driven by some elegant and compelling research from a range of cohort studies involving African prostitutes multiply exposed to HIV-infected clients, seronegative babies born to seropositive mothers, and non-progressors, who have been infected but do not progress to full-blown AIDS," he said.

"The consensus is that, if anything is consistent, all these associations involved demonstrable cell-mediated immune function. By extension, you need to design a vaccine specifically to induce a cell-mediated response.

"But it's also absolutely clear that, whatever its capacity to induce substantial cell-mediated immunity, a vaccine also must also induce a strong antibody response. By definition, cell-mediated immunity only works against cells that have already been infected, so it won't stop people becoming infected.

"That's a substantial challenge, but there are some technologies around. We're about to begin a Phase I clinical trial of a 'prime and boost' vaccine in human volunteers.

The prime and boost technique involves doubly injecting subjects with naked DNA sequences for selected HIV antigens, then later injecting the peptide antigens themselves to 'boost' the response.

Immune responses

Commenting on evidence for significant differences in antibody responses in the racial or ethnic sub-groups involved in the US trial, Dr Stephen Kent, a virologist with the University of Melbourne Department of Microbiology and Immunology, said there were known differences in immune responses between such groups.

"But drawing conclusions from sub-group analyses is always risky," Kent said. "There have been many cases in which something seen in a sub-group analysis has not been confirmed by subsequent, more detailed study."

Kent said that even though the vaccine targeted the B strain of the HIV virus, the potential presence different sub-types in the different cohorts was potentially a confounding factor in the reported results.

Prof Roger Short, an internationally renowned expert on human sexual behaviour at the Royal Women's Hospital in Melbourne, said he doubted claims for statistically significant differences in protection levels between the different cohorts involved in the trial.

"I'm not surprised that it didn't work," he said. "We were told at the World AIDS conference in July that, despite our best hopes, vaccines were looking increasingly disappointing.

"We desperately need a vaccine," said Short. He said VaxGen had made a brave attempt, but vaccine studies of this type were "incredibly difficult" to do because of confounding factors."