AIDSWEEKLY Plus; Monday, September 28, 1998
Daniel J. DeNoon, Senior Editor
This is the message for both sides in the increasingly vituperative debate over possible human trials of a live attenuated AIDS vaccine. The message comes from the man responsible for developing the vaccine.
A debate over the issue at the recent XII World AIDS Conference in Geneva demonstrated the high level of emotion among well-meaning researchers on both sides of the issue (see AIDS Weekly Plus, August 24, 1998).
"Recent discussion of using live attenuated HIV-1 strains as a vaccine approach for AIDS seems to be raising blood pressures to unusually high levels," noted Harvard researcher Ronald C. Desrosiers in a letter to the journal Nature Medicine ("Prospects for Live Attenuated HIV," Nature Med, 1998;4(9):982).
Desrosiers did not participate in the debate over human tests of a vaccine based on the prototypes he has been testing in monkeys for nearly a decade. But his letter clearly stakes out a middle position between those urging immediate human trials and those who flatly state that no live retrovirus vaccine can ever be safe enough.
He suggested that important questions about a live attenuated HIV vaccine can be answered without putting humans at risk.
"We may not yet be ready for testing of live attenuated HIV-1 strains in human volunteers, but the scientific method that has been moving forward needs to run its course," he argued. "Large-scale, placebo-controlled safety testing of a multiply deleted SIV vaccine in hundreds of rhesus monkeys needs to be an important priority for the coming year."
Although he avoided mentioning Robert Gallo by name, Desrosiers decried "the oft repeated statements 'I never met a retrovirus that didn't cause disease,' and 'All retroviruses will cause disease eventually.'" Gallo vehemently expressed this opinion during the AIDS conference debate.
"These statements are at best misleading, but closer to simply wrong; there are many examples to the contrary," Desrosiers wrote. He noted that most animals inoculated with live SIV lacking the nef or nef plus vpr genes maintain undetectable viral loads throughout follow-up.
"The oldest nonprogressing survivors have now lived nine years, about 50 percent of the lifespan of an aged rhesus monkey," he wrote.
Desrosiers warned about oversimplifying discussion of a live AIDS vaccine by considering nef-deletion as the only available attenuation.
"There is a big difference between the attenuated SIV strains that have induced disease in a small percentage of monkey recipients and the much more highly attenuated strains that have been the focus of current research," he wrote.
As has often been noted, no other vaccine approach has demonstrated anything close to the level of protection offered by live attenuated vaccine against the pathogenic SIV strains that bear the most resemblance to pathogenic HIV-1. Desrosiers openly hoped that a safe, recombinant vaccine can be found that will offer risk-free protection capable of meeting the urgent need for an AIDS vaccine.
"But if the vaccine approaches now being forwarded prove to be as ineffective as many predict, we should be prepared to consider some calculated risks," he concluded.
Correspondence regarding the letter may be addressed to Ronald C. Desrosiers, Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102. Email: <rdesrosi@warren.med.harvard.edu>.
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