AIDS vaccine: research on target.

AIDS Vaccine: Research on Target

Since the AIDS virus, now known as HIV, was first identified in 1983, more than a half-dozen related viruses have come under scrutiny by scientists trying to understand HIV's mechanism of infection. Two previously unknown relatives of HIV have also been discovered (HIV-2 and STLV-III), leaving researchers awash in an alphabet soup of distinct but related viruses--including some that infect humans, some that are restricted to monkeys, some that cause disease and some that apparently do not. The genetic diversity displayed by the HIV family, and the fact that HIV itself fails to cause AIDS in other animals, has hampered the study of the disease and the search for a vaccine (SN: 5/9/87, p.297).

But two new studies published in the Aug. 6 NATURE go a long way toward sorting out the relationship among these viral varieties. Moreover, they offer hope that AIDS vaccine development may proceed more rapidly than was anticipated.

Researchers at the National Cancer Institute (NCI) report that they have determined the entire 9,264-nucleotide sequence that makes up the genome of an AIDS-like virus found in African green monkeys. The researchers, Genoveffa Franchini, Robert C. Gallo and their colleagues, then compared that sequence to the genetic codes of previously cloned AIDS-related viruses. They found that the newly sequenced STLV-III(AGM) virus, although apparently nonpathogenic in green monkeys, is genetically very similar to HIV-2 (the cause of AIDS in West Africa) and is to a lesser extent related to HIV-1 (the cause of AIDS in the United States).

The new analysis resulted in two important findings. First, the scientists identified genetic variations that may explain why certain strains of AIDS-like viruses do not cause disease. Second, and more important from the standpoint of vaccine development, they found striking similarities within certain geomic regions that code for the production of viral envelopes, or outer skins, of the strains they compared. In almost all cases, for example, the nucleotides that code for the amino acid cysteine are located in exactly the same positions on the genome. This is true even in strains whose genomes otherwise vary by as much as 25 percent.

Researchers theorize that such highly conserved regions are critical to the process of infection--perhaps enabling the virus to bind to the T4 antigen on human lymphocytes. Because so many strains of AIDS-related viruses share these nucleotide sequences, the proteins they code for may be ideal targets for antibody tests and vaccines.

In related research, Pierre Tiollais and others at the Institut Pasteur in Paris say they have cloned and sequenced the entire genome of a virus that causes an AIDS-like disease in macaque monkeys. The virus, STLV-III(MAC), is the only virus that is known to share most of the properties of human AIDS-causing viruses and that actually causes an AIDS-like disease in animals. The accomplishment opens the door to preliminary tests of recombinant vaccines on animals.

Animal models are considered essential for testing potential vaccines, but until now scientists have been frustrated by the lack of an appropriate animal to work with. Chimpanzees, although they can harbor HIV, are in short supply, and in any case fail to develop AIDS when infected. Although the STLV-III(MAC) virus differs somewhat from human AIDS-causing viruses, it has several genetically conserved regions identical to some regions in HIV-1 and HIV-2. Scientists hope to test a variety of STLV-III(MAC) antigens as potential vaccines in macaques, and then --by referring to the newly created nucleotide map--test analogous HIV antigens in humans.