Apr. 23, 1998 A vaccine pairing a genetically altered, harmless canarypox virus, and a genetically engineered piece of the HIV protein coat, induce immune system activity against laboratory strains of HIV better than either vaccine alone, according to a Johns Hopkins School of Public Health researcher.
"The results of tests on 131 people at low risk for HIV infection convinced us we should continue testing two-vaccine combinations," says Mary Lou Clements-Mann, M.D., M.P.H., professor of international health and lead author of a report on the multicenter trial published in the May 1998 issue of The Journal of Infectious Diseases. The study was supported by the National Institutes of Health.
The researchers are now conducting further trials in which canarypox vaccines with genes for HIV envelope protein -- a piece of the outside covering of the virus -- and other HIV gene products are given together or in sequence. These vaccines also are being tested in volunteers at high risk for HIV infection due to unsafe sex or other behaviors, according to Clements-Mann.
The combination vaccines stimulated anti-HIV immune system activity in volunteers better than either vaccine alone, sparking production of both anti-HIV antibodies and CD8+ cytotoxic T lymphocytes (CTLs), white blood cells that destroy cells infected with the HIV virus, says Clements-Mann.
The multicenter team tested the two-vaccine combination -- called ALVAC-gp160/rpg120 -- because previous research suggested that a successful AIDS vaccine might need to induce both antibodies and CD8+ CTLs to eliminate HIV from the body. Past vaccines made with altered live vaccinia viruses expressing HIV proteins could potentially spread from person to person and possibly harm persons with AIDS, according to Clements-Mann. But the genetically engineered canarypox viruses do not multiply in humans, she says. "Therefore, we believe these vaccines will be safe and not be transmissible to people vaccine volunteers are in contact with."
The ALVAC-gp160 protein made from the canarypox virus, the "prime" vaccine used in the study, was given twice to stimulate production of CD8+ CTLs and prime the immune system for producing HIV antibodies. The rgp120 vaccine was then given to boost antibody production.
In some volunteers, ALVAC-gp160 given four times, without the rgp120 booster, induced antibody production, but at a much lower level.
The team also found that people previously immunized with smallpox vaccine (vaccinia virus) responded to the canarypox vaccine just as well as those who had never received smallpox vaccine.
The researchers tested two dosages of ALVAC-gp160 given alone four times or given twice, followed by two immunizations with rgp120. Another group received rgp120 alone four times. All 38 volunteers immunized with both vaccines produced anti-HIV antibodies that killed -- or neutralized -- HIV strains in the test tube, while 19 of 31 volunteers given ALVAC-gp160 alone, and eight of nine given rgp120 alone, produced neutralizing antibodies.
The researchers detected anti-HIV CD8+ CTL activity mainly in volunteers getting ALVAC-gp160 alone (four of 18 recipients), or in combination with rgp120 (seven of 19). Only one in 10 volunteers who got rgp120 alone had CD8+ CTL activity.
Other authors of the study include Kent Weinhold, Thomas J. Matthews, Barney S. Graham, Geoffrey J. Gorse, Michael C. Keefer, M. Juliana McElrath, Ray-Hahn Hsieh, Jiri Mestecky, Susan Zolla-Pazner, John Mascola, David Schwartz, Robert Siliciano, Lawrence Corey, Peter F. Wright, Robert Belshe, Raphael Dolin, Susan Jackson, Serena Xu, Patricia Fast, Mary Clare Walker, Don Stablein, Jean-Louis Excler, James Tartaglia, Anne-Marie Dullege, Fauk Siinangil, Enzo Paoletti, and the National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.
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