AIDSWEEKLY Plus, 22 July 1996
Daniel J. DeNoon, Senior Editor

Like the mythological figure Tantalus who starves with food dangling just out of reach, the vast majority of people with AIDS will never see the protease inhibitors that have stolen the show at the XI International Conference on AIDS, held July 7-12, 1996, in Vancouver, British Columbia, Canada.

The one great hope is the development of an AIDS vaccine capable of preventing, and perhaps even treating, HIV disease.

"Vaccines will be overshadowed by developments in antiretrovirals, but remain the main issue for the developing world," said Swedish AIDS researcher Eric Sandstrom.

U.S. researchers agree, according to Vanderbilt University researcher Barney Graham, speaking on behalf of the National Institute of Allergy and Infectious Diseases' AIDS Vaccine Evaluation Groups (AVEG).

"Vaccine development is still the key to eradicating the epidemic," Graham said.

As debate continues over when early candidate HIV vaccines should be tested in advanced clinical trials (see the accompanying article), the U.S. vaccine research effort remains focused on less flashy but, according to Graham, crucially important smaller trials.

"We see Phase I and Phase II trials as central to vaccine development," Graham said.

In a conference presentation, Graham listed some of the important advances already achieved in the AVEG program:

• More than 1,900 subjects have enrolled in U.S. Phase I and II trials.
• More than 30 studies have evaluated 16 different vaccine antigens, 12 adjuvants, and "a variety of delivery vehicles, immunization routes, and schedules."
• The only adverse events to date have been limited, local reactions to vaccines and adjuvants.
• gp120 subunit vaccines elicit neutralizing antibodies against HIV isolates grown in laboratory culture, but not against primary isolates isolated from patients.
• Vaccines based on the HIV gp120 envelope glycoprotein elicit more neutralizing antibodies than vaccines based on the gp160 envelope precursor glycoprotein, but gp160 vaccines elicit more binding antibodies.
• Monthly peptide inoculations are not as effective as schedules incorporating a rest interval.
• A fifth dose of a peptide vaccine does not increase antibody titers beyond levels previously achieved, but is able to restore fading titers to previous levels.
• The prime/boost approach - using a recombinant vector for priming followed by booster inoculation with peptide vaccine - elicits a good anti-HIV cytotoxic lymphocyte (CTL) response.
• The booster response in vaccinees primed with a recombinant vector is improved with increased time between priming and boosting.

"Rather than single-product regimens, the focus is now on complex vaccine vectors in combination with other products used to boost selected components of the immune system," Graham said.

There have been no headlines, Graham admitted, but the program has achieved progress in small increments.

"Ultimate success will require cooperation among groups with diverse scientific and social perspectives," he said. "Continuing evaluation of modern vaccine concepts in humans and basic investigation to define mechanisms for inducing HIV- 1 immunity will be needed."

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