Human AIDS vaccines: mice offer shortcut.

Human AIDS vaccines: Mice offer shortcut 

Using a novel strain of mice, scientists may learn within the next few weeks whether humans inoculated with the first U.S.-tested AIDS vaccines can indeed resist infection with the AIDS virus (HIV). If the mouse assay works, it may cut years off the time required to get evidence of AIDS-vaccine efficacy in humans, the researchers say.

Scientists currently are conducting U.S. clinical trials of two AIDS vaccines, using uninfected men at high risk of acquiring the disease. Some have responded by producing antibodies, but researchers don't know whether these antibodies can fight off an actual infection. And because AIDS develops so slowly in humans, investigators have anticipated a three- to five-year wait for efficacy data -- even if some of the men acquire the infection soon after vaccination.

Donald E. Mosier, an immunologist at the Medical Biology Institute in La Jolla, Calif., says he now hopes to gain evidence of vaccine efficacy long before that by enlisting the help of hu-SCID mice -- a strain he and his colleagues engineered to contain human immune systems (SN: 9/24/88 p. 198). Previous work has shown that the mice can become infected with HIV, but unlike humans they develop symptoms within weeks after infection.

Mosier says he has taken blood from men inoculated with either of the U.S. experimental vaccines and transfused it into several hu-SCID mice. Six weeks ago, his team challenged these mice with doses of HIV. By watching for signs of disease over the next four weeks, the scientists should get a good indication of the vaccines' protective value, Mosier said in New Orleans this week at the annual meeting of the American Association for the advancement of Science.

AIDS researchers express a growing belief that vaccine development may ultimately prove more important than drug treatment in stemming the global epidemic. The new emphasis builds upon promising vaccine studies in monkeys (SN: 12/9/89, p. 372) and the recognition that most people with AIDS -- both in the United States and abroad -- are too poor to afford AIDS drugs. "Unless we come up with a vaccine, the future of this epidemic worldwide is extremely grim," says William Haseltime of the Dana-Farber Cancer Institute in Boston.

Mosier reports that his team's work with the hu-SCID mice has already identified experimental AIDS drugs that appear more potent than zidovudine (AZT), the only AIDS drug now licensed in the United States. The group has also provided some hu-SCID mice with blood and immune cells from HIV-infected human newborns to create a animal model for pediatric AIDS. And with researchers at the National Institutes of Health, Moiser has created a gene-altered hu-SCID mouse that secretes constant supplies of an experimental AIDS drug called soluble CD4 (SN: 2/17/90, p.101) into its bloodstream. Some scientists anticipate a future in which altered human cells will produce constant supplies of CD4 in people infected with HIV.

Among other AIDS developments discussed at this week's meeting:

* Haseltine described ongoing work aimed at removing the genetic material from HIV to create an "eviscerated" version of the virus. He wants to fill the viral shell with an HIV-killing toxin, in hopes that the shell will serve as a Trojan horse capable of finding and killing white blood cells infected with real viruses.

* Norman L. Letvin of the Harvard Medical School in Boston dampened the enthusiasm some have expressed about the prospects of using soluble CD4 to deliver toxins to HIV-infected cells. He exposed cultured, HIV-infected human lymphocytes to soluble CD4 molecules bound to a powerful, bacterially produced toxin. The combo killed many infected cells. Letvin says, but it apparently left some HIV reservoirs intact. Once the researchers discontinued the treatment, HIV began to multiply again. Although CD4-bound toxins may someday prove useful in conjunction with other approaches, he concludes, "I'm not very optimistic" about its value alone.