Jose Esparza (photo © Julie Clayton)

There is no substitute for multiple clinical trials of HIV vaccines in humans, even in the face of uncertain results from animal studies, argues a leading director of the World Health Organization (WHO).

"We're not doing enough to develop an anti-HIV vaccine," today declared Jose Esparza, co-ordinator of the Global Program on AIDS vaccines at the WHO Joint UN Program on HIV/AIDS. He is frustrated by the recent US decision to cancel a major HIV vaccine trial.

According to WHO statistics, the HIV epidemic has already killed around 20 million people, and another 40 million are infected. "I would not be surprised if it did not become the world's greatest killer," he said.

Speaking on "the search for an anti-HIV vaccine," Esparza argued that the answer could already lie in existing vaccine candidates. What's urgently needed, he says, is to go ahead with multiple efficacy trials of vaccines involving different HIV strains, in different populations, with different genetic backgrounds.

At least 30 different vaccines have now been investigated in more than 60 small-scale safety trials, involving 10,000 HIV negative volunteers. But without taking these further into larger phase III efficacy trials, they do not answer the critical question of what protects.

Esparza criticized the decision two weeks ago by the US National Institutes of Health to cancel a planned phase III vaccine trial. This would have tested the ability of a prime-boost strategy, using a canary-pox vector together with the HIV envelope protein gp120, to trigger both cytotoxic T cells (CTL) and antibodies.

NIH officials justified their decision by saying that the vaccine had failed to produce CTL in more than 30% to 40% of volunteers, in a smaller study. This was despite the production of antibodies in 100% of individuals.

It would still have been worth forging ahead, even in the face of sub-optimal CTL responses, as these may still prevent infection, argues Esparza. And if not prevention, they may reduce viral load sufficiently to decrease transmission between people, he adds.

Either way, Esparza insists, the trial would have given valuable information.

The trial was to have taken place in the US, South America and the Caribbean, in 11,000 volunteers. Meanwhile, another trial of a similar vaccine, sponsored by the US Department of Defense, will still go ahead in Thailand, in 16,000 volunteers, starting in 2003.

Some have argued that the two trials were overlapping in their intent, and that conducting both would have been a waste of money. Not so, according to Esparza. The Thailand trial is about prevention, while the US trial is about the relative contributions of antibodies versus CTL to protection, he says. Both trials are vital, he adds.

Dozens of candidate HIV vaccines have undergone tests in chimpanzees and macaque monkeys. But these models have so far failed to indicate exactly what is needed in order to protect against infection.

"We still do not know what are the correlates of protection," and only human trials can provide this information, Esparza said.

And cost is not an issue: vaccine research is extremely under-funded compared with the amount of money spent on anti-retroviral drugs, he asserts.

"People think that everything is being done to try to develop a vaccine, but that is not true," he told BioMedNet News. For example, the global investment in vaccines is currently $500 million, the same amount that Brazil, a single developing country, is spending on anti-retrovirals, he says.