Embargoed for Release
January 31, 2000
5 p.m. Eastern Time
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FINDING MAY LEAD TO NEW APPROACH FOR PREVENTING MOTHER-TO-INFANT HIV TRANSMISSION DURING BIRTH
Combination of antibodies shown to block transmission of HIV-like virus across mucous membranes
BOSTON - In Africa, where tens of thousands of children infected with the AIDS virus are born each year, a drug or vaccine capable of preventing the virus from passing from mother to infant has the potential to save many lives.
In a new study published in the February issue of Nature Medicine, researchers at Dana-Farber Cancer Institute (DFCI)--in collaboration with colleagues at the Department of Veterinary Services, University of Texas M.D. Anderson Cancer Center--suggest it may be possible to protect infants from acquiring the virus during birth by giving them and their mothers a combination of three potent human antibodies shortly before delivery and after birth.
The new approach, known as passive immunization, was tested in monkeys that were later exposed to a virus containing parts of the human and monkey AIDS viruses. The antibodies were so effective at neutralizing the virus that throughout six months of observation, none of the monkeys in the study had detectable levels of virus in their blood.
"This demonstrates the principle that passive immunization with these antibodies can protect against HIV transmission during delivery and birth," says the study's senior author, Ruth Ruprecht, M.D., Ph.D., of Dana-Farber and Harvard Medical School (HMS). "If this approach works as successfully in humans, and if the antibodies can be produced inexpensively, it may offer a practical way of preventing mother-to-infant transmission of the AIDS virus even in the developing world."
Previous research has shown that although HIV can pass from mother to infant during pregnancy, birth, or by breast feeding, the most common time is shortly before or during delivery. There is indirect evidence that the virus can be transmitted from the infected mother to the infant as it passes through the birth canal.
Attempting to block that transmission with antibodies has met with much scientific skepticism in the past. Antibodies are proteins produced the by immune system that attack dangerous viruses by locking onto key structures, called epitopes, on the viruses' surface. The coat protein of HIV, however, is covered with so many sugar molecules that antibodies have a hard time finding its important epitopes and blocking virus entry into the cell. As a result, neutralization of HIV by antibodies tends to be rather weak and ineffective.
For the current study, the Dana-Farber researchers used three antibodies from people who had been infected with HIV, but whose antibodies had proved unusually effective in blocking HIV replication. In laboratory studies, the three antibodies had been shown to work synergistically - that is, they enhanced one another's ability to neutralize the virus when used together.
To determine whether the antibodies could thwart mother-to-infant transmission of the virus, the researchers gave a triple combination of the antibodies intravenously to four pregnant monkeys five days before delivery and three days afterwards. An hour after the second infusion, the adult animals were given intravenous doses of a virus called SHIV-vpu+, which combines the core of SIV, the virus that causes AIDS in primates, with the protein coat of HIV, which causes the disease in humans.
Tests of the animals' blood over the next six months showed all four to be free of SHIV-vpu+ infection.
The infant monkeys received the antibodies shortly after birth and, one to four hours later, SHIV-vpu+ was given by mouth, a process that mimics the transmission of HIV from the mothers' tissues to the infants. Eight days after that, the monkeys were again given the triple combination of the antibodies. A separate set of four newborn monkeys were given SHIV-vpu+ by mouth without receiving the antibody treatment.
In blood tests conducted over the next six months, the untreated infants were found to have persistent SHIV-vpu+ infection. The antibody-treated infants, by contrast, had no traces of the virus.
"This is the first demonstration that a triple combination of human antibodies can protect infants from contracting AIDS virus at birth," Ruprecht says. "The three antibodies appear to home in on regions of the HIV coat protein that are essential for virus replication.
"By understanding how these antibodies protect against viral transmission across mucous
membranes, we may gain insights that can be used to develop a safe, effective AIDS vaccine," she continued. "More immediately, passive immunization needs to be studied as a promising means of protecting infants from HIV infection during birth."
This international, multi-institutional collaboration involved the following researchers: Timothy W. Baba (DFCI, HMS, Tufts University); Vladimir Liska, Regina Hofmann-Lehmann, Josef Vlasak,Weidong Xu, Marshal Posner, Joel E. Wright and Seyoum Ayehunie (DFCI, HMS) Lisa A. Cavacini (Beth Israel Deaconess Medical Center, HMS); Herman Katinger, Gabriela Stiegler (Institute of Applied Microbiology, Vienna, Austria); Bruce J. Bernacky, Tahir A. Rizvi, Russell Schmidt, Lori R. Hill and Michale E. Keeling, (Dept. of Veterinary Sciences, University of Texas, M.D. Anderson Cancer Center); Yichen Lu (Harvard School of Public Health); and Ting-Chao Chou (Memorial Sloan-Kettering Cancer Center).
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