Harvard AIDS researchers working with monkeys say the virus overcame an experimental vaccine by changing a single gene, killing one of the 8 animals being tested. This disappointment doesn?t mean that AIDS vaccines are doomed to fail, but it illustrates how hard it will be to produce one.
HIV is already is known to mutate and become resistant to standard AIDS drugs in at least half of all Americans who have the infection. Now researchers have seen a similar outcome with an experimental vaccine that tries to stimulate immune cells to prevent the virus from multiplying.
?It is sobering to find that a single-point mutation within the virus can initiate a cascade of events resulting in a clinical vaccine failure and death,? says Dan H. Barouch, of Harvard Medical School, who is leading the study.
More than one dozen experimental vaccines using different genetic strategies have been tested in various laboratories. Some have been successful for more than two years. Unlike a flu shot, AIDS vaccines do not actually prevent infection by stimulating antibodies that neutralize the invading virus. HIV comes in many strains and it changes rapidly, so it would overwhelm the antibody response.
Instead, the AIDS vaccines work by holding the HIV infection in check. The vaccines are made with genes that carry the code for proteins in the virus. When the immune system sees these codes, it stimulates production of a broad class of virus-fighting cells known as T cells.
In another study, researchers at Merck Pharmaceuticals have seen no signs of the Harvard problem, known as ?gene-escape.? ?We?ve gone 500 days and not seen any escape,? says molecular biologist Emilio Emini, director of the trials. ?It?s something to watch for. But if the vaccine elicits a sufficiently broad genetic response, this is going to be an issue that we can deal with.?
Developing an AIDS vaccine will be ?an uphill grade for the foreseeable future,? says Jeffery Lifson of the National Cancer Institute.
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Researchers are still looking for the origin of AIDS, and for the first time they have found an HIV-like virus in a single chimpanzee in the wild, in a different part of Africa than they?d suspected.
This type of chimpanzee in Tanzania could not be the source for human AIDS, because the viral strain the researchers found is too genetically different. But now that they've proved virus testing can be successful in the jungle, Dr. Beatrice Hahn of the University of Alabama and her team will begin tracking different chimps in even more remote parts of Africa, where the virus is thought to have jumped from animals to man.
Scientists have long known nonhuman primates carry their own version of the AIDS virus. But so far, it has been found only in captive chimpanzees. No one knows how prevalent or geographically or genetically diverse the virus is in chimps in the wild. ?Study in the wild is a very difficult thing. You can?t just walk in there and ask them for a blood sample,? says Hahn.
Many scientists believe HIV probably originates from SIVcpz, a strain of simian immunodeficiency virus found in a subspecies of chimpanzee from west-central Africa. Hahn?s research team developed a highly sensitive test to check urine and fecal samples for antibodies against SIV, and learned how to find samples in the jungle. They enlisted help from primatologists, including Jane Goodall, who have extensively monitored chimp colonies in Tanzania, Uganda and the Ivory Coast. The primatologists can identify these chimps by sight, meaning Hahn can find out exactly which animal has SIV if any samples test positive.
Of the 58 animals tested, only one had SIVcpz, a healthy 23-year-old male in the Goodall colony in Tanzania. Primate carriers of HIV to not become sick from AIDS themselves; they are only hosts for the virus. This animal?s strain was so genetically different that it rules out east African chimps as HIV?s source.
Captive animals that harbor the virus that is most like human HIV are a subspecies from countries farther west, Gabon and Cameroon. Those animals are very shy and primatologists haven?t been able to do studies like Goodall?s. Finding the virus in those animals would strengthen the AIDS origin theory.
The Tanzanian find is important because the animal?s viral strain isn?t strong enough to infect his sexual partners. Hahn says that if we can understand why, ?we can get some clues that will help us combat HIV better in humans.?
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