Finding May Be a Step Toward AIDS Vaccine
In a finding that could help in the development of an AIDS vaccine, researchers for the first time have immunized monkeys against infection by a distant relative of the AIDS virus that causes a rare form of leukemia.
The virus used in the vaccine, HTLV-1, has also been linked to multiple sclerosis, systemic lupus erythematosus, and certain other rare neurological conditions, and is endemic among intravenous drug users in certain eastern urban areas such as New York City.
Spreading Virus
The HTLV-1 virus is spread by the exchange of body fluids in the same fashion as the AIDS virus, and federal officials last year estimated that 2,800 people could be infected with it each year as a result of blood transfusions. During the last two months, the American Red Cross began screening all donated blood for the presence of the virus.
Insights gained in the current research, which was done at Ohio State University, may show researchers which components of the AIDS virus must be present in a vaccine, according to Ohio State pathobiologist Richard G. Olsen.
Olsen estimated that at least three years of further studies will be required before the vaccine can be tested in human beings.
The Olsen group’s research is “simply fascinating,” said neurologist Steven J. Greenberg of the National Cancer Institute in Bethesda, Md. “I think it is going to be a source of great excitement in the neurological and virological communities.”
HTLV-1 (human T-lymphotrophic virus-1), discovered in the early 1980s by virologist Robert C. Gallo of the National Cancer Institute, is a member of an unusual family of viruses called retroviruses. Unlike most disease-producing viruses, whose genetic information is contained in the form of deoxyribonucleic acid (DNA) like that found in all animal and human cells, retroviruses encode their genetic information in ribonucleic acid (RNA).
When a retrovirus infects a cell, a special viral enzyme must convert the RNA information into DNA before the virus can reproduce.
Of the Same Type
The AIDS virus is also a retrovirus, as is the feline leukemia virus, which is the No. 1 killer of domestic cats in the United States. Olsen and his colleagues previously developed a vaccine against the feline leukemia virus that is now widely used to protect pets, and they used the same technique to develop the HTLV-1 vaccine.
HTLV-1 has been shown to cause adult T-cell leukemia and lymphoma, which are rare in the United States but are more common in Japan, Central Africa and the Caribbean basin. In January, Greenberg and a group from the Wistar Institute in Philadelphia reported independently that they had found traces of HTLV-1 or a virus very much like it in many patients with multiple sclerosis, a chronic disease of the central nervous system that afflicts about 250,000 people in the U.S.
Olsen has found traces of the virus in patients with lupus, an autoimmune disorder in which the victims’ immune systems attack their connective tissues and internal organs. The virus has also been linked to exotic disorders, such as tropical spastic paraparesis, in which nerves on the limbs become paralyzed.
Olsen’s vaccine does not contain the virus itself, but proteins that are secreted by HTLV-1-infected animal cells that are grown in the laboratory. The proteins he uses are precursors of the viral proteins--that is, large proteins that must be trimmed by cellular machinery before they can be incorporated into viruses.
Greater Immune Response
In the development of the feline leukemia virus, Olsen found that these precursor proteins produce a greater immune response than the viral proteins themselves and are less likely to produce harmful effects.
Both the cat vaccine and the HTLV-1 vaccine, furthermore, contained proteins from both the outer coating of the virus particle and the inner core. That is an important finding, Olsen argued, because most potential AIDS vaccines now being studied use only one type of protein or the other, and are thus less likely to be effective. “More than one protein is going to be necessary” for an AIDS vaccine, he said in a telephone interview.
Olsen injected nine macaque monkeys with the vaccine, then inoculated them and five nonvaccinated monkeys with STLV-1, a virtually identical monkey equivalent of HTLV-1. (The researchers used STLV-1 to ensure that the vaccination had not simply stimulated immunity to human products.)
The unvaccinated animals, he reported at a recent meeting on retroviruses, all became persistently infected with the virus, showing virus activity in their white blood cells.
Monitored for Two Years
But white blood cells from the nine vaccinated monkeys showed no evidence of viral activity, suggesting that the vaccine protected them from the virus. Some of the monkeys have been monitored for as long as two years without any traces of infection.
Greenberg and others have cautioned that further studies are necessary because HTLV-1 can insert its genetic information into the host cell’s genes and remain hidden for two to four decades before triggering an active infection. Olsen agrees, and is now using sophisticated genetic engineering techniques to search for the viral genes in white blood cells from the vaccinated monkeys.
UCLA hematologist Irvin S. Y. Chen warned that Olsen will have to conclusively demonstrate the safety of the vaccine before it can be tested in humans. Only about 1% of people infected by the virus actually develop disease, he said, so a vaccine would have to have a very low incidence of side effects to justify using it.
