AIDS vaccine research: promising protein.

AIDS vaccine research: Promising protein

A viral antigen that "does the right stuff" has brightened hopes for the development of an AIDS vaccine, government scientists said at a press briefing last week.

The antigen, a protein from the outer coat, or "envelope," of the AIDS retrovirus, triggered an immune response when injected into animals, report researchers at Duke University in Durham, N.C., and the National Cancer Institute (NCI) in Bethesda, Md. That finding was encouraging in itself. Beyond that, however, what one researcher calls "the right stuff" made itself apparent when the antibodies made by the animals neutralized AIDS virus in the test tube.

Thus far, researchers have induced antibody formation in goats, rabbits, mice and guinea pigs. They have begun tests on rhesus monkeys to see if the protein, called gp120, will similarly prod a primate immune system into making the neutralizing antibodies. But since none of these animals is susceptible to human AIDS, the real test of the antigen's potential as a vaccine will come with chimpanzees, who are vulnerable to the virus. The researchers hope that exposure to the antigen alone will have the chimpanzees' immune systems revved up and ready with antibodies, able to neutralize the virus before it can invade the animals' cells.

Antibodies with at least a slight ability to neutralize the AIDS virus in the test tube have been found in the blood of some AIDS and "pre-AIDS" patients (SN: 7/20/85, p. 40). Clearly, the antibodies found in AIDS patients have been ineffective against the virus. But, says Donald Francis of the Berkeley, Calif., office of the Centers for Disease Control, the situation in AIDS patients is "very different from pre-exposure presentation [of the antigen] to an individual who has not seen the virus, and whose system has not been deranged by the virus."

Antibodies formed in the body are a response to the living, whole virus. But researchers can't use the whole virus as a vaccine, even if it is killed, because of a double risk: The virus might revitalize itself, and the incorporation of viral genes into cellular DNA might at some point trigger cancer. Instead, researchers have looked for nongenetic bits of the virus, like gp120, that the immune system recognizes as foreign.

Even if gp120 protects chimpanzees against AIDS, there are still potential roadblocks. Most worrisome is the variability of the virus: Will an antigen that comes from one viral strain, and confers immunity against it, give any protection against another?

Research has focused on the envelope protein in part because something on the outer coat of the virus must remain constant if the virus is to continue to recognize and bind with its host cells. While gp120 is one of the most variable of the viral proteins, there are stretches within it that remain unchanged throughout the different viral strains.

"The question is," says Francis, "are those conserved regions important in producing neutralizing antibodies?" If they are, gp120 from any strain might elicit antibodies that recognize the protein of any other strain. Hepatitis B, for example, is a virus with multiple sub-types, but with enough stability among the strains that one vaccine protects against all of them. Even if the antibodies turn out to be strain-specific, gp120 may still be useful, says Peter Fischinger of NCI's Frederick (Md.) Cancer Research Center. "With some retroviruses," he says, "we have seen that as you continue immunizing, the neutralizing response becomes broader."

The earliest possible testing of an AIDS vaccine in humans would be in 1988, according to Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "You're going to have to tack on at least a few years more," he adds, because the disease's long latency period will increase the time necessary to determine the vaccine's efficacy.