McElrath to speak on progress toward an HIV vaccine

Juliana McElrath

By July 2000, clinical human trials are set to begin at the UW and other research centers in the country that may prove we can stop HIV-1, the virus that causes AIDS, in its tracks. The trials will test the effectiveness of a vaccine against the disease.

Since the late 1980s, approximately 30 different vaccine trials have been conducted in Seattle and the five other centers that make up the NIH-supported AIDS Vaccine Clinical Trials Network. Only two of these trials have made it to the Phase II level. The fact that we will see a study by 2000 that takes the next step is an achievement, said Dr. Juliana McElrath, an associate professor of medicine at the UW and member of Fred Hutchinson Cancer Research Center, who will lead the study.

For some of the 600 people who have participated in trials in Seattle, the HIV-1 vaccine has appeared to stimulate immunity. But McElrath stressed that the missing key right now is quantitative data. Is the vaccine preventing infection in enough people to prove it is effective?

To date, the vaccines have been given mostly to low-risk volunteers. In the July 2000 trials, however, researchers will be testing the effectiveness of the vaccine in large numbers of high-risk volunteers.

McElrath will discuss the research behind the development of the vaccine as well as other aspects of her research in a Science in Medicine Lecture, titled “Can We Protect Against HIV-1 Infection?,” on Friday, Feb. 12, from noon to 1 p.m. in room T-625 of the Health Sciences Center.

As an infectious diseases specialist, McElrath was taking care of patients with AIDS when the epidemic began in the mid 1980s. Witnessing the rampage of the disease led her to research to stop it. In 1990, she joined the vaccine program established at the UW by Dr. Lawrence Corey, professor of laboratory medicine and head of the department’s Division of Virology.

The vaccine currently being used in trials is a canarypox virus in which researchers have implanted specific HIV-1 genes. When the volunteer is injected with this harmless virus, his or her immune system responds by creating killer T-cells to fight it. When, or if, this inoculated person is infected with HIV-1, his or her immune system “recognizes” it early and again launches these waves of T-cells to kill it.

“To develop the components for a vaccine, we’ve had to understand what happens early on during the infection,” McElrath said.

Part of McElrath’s research is the study of a group in the Seattle area who are at high risk of exposure to HIV due to sexual behavior or intravenous drug abuse. Because of the group’s low rate of infection, McElrath suspects they may have developed immunities that make them more resistant to HIV-1.

In the last few years, genetic research has suggested that mutations of certain T-cell receptors may give a person “relative resistance” to the virus, McElrath said. CCR5 is the name of one receptor on the surface of T-cells which HIV-1 targets as an entry-point for its invasion of the cell. People with genetic mutations of these receptors tend to become less infected.

Yet, McElrath’s group of high-risk individuals in Seattle do not have an unusual number of these genetic mutations. McElrath said she suspects that their immune systems are somehow maintaining responses based on previous exposures to the virus, or that they have been exposed to a weakened virus.

McElrath and her colleagues have struggled to detect HIV-1 in people whom they suspect have been exposed to the virus, usually from a sexual partner, because they believe the virus may still be lurking. “It is possible for HIV to be hiding in resting T-cells,” she said. Researchers have had to come up with newer and more sensitive methods for detecting the virus.

Research has also revealed that killer CD8 cells are present in mucosal tissue in the cervix and vagina, and in semen, and that people with higher levels of these cells are less frequently ill with their HIV infection. If the response of these CD8 cells can be increased within a short time after infection, McElrath said, researchers may be able to develop methods to impact the virus locally to control its spread.

McElrath received an M.D. and Ph.D. from Medical University of South Carolina in 1980. She joined the UW School of Medicine from The Rockefeller University in 1990 as an assistant professor of medicine in the Division of Allergy and Infectious Diseases. She was named co-director of the UW AIDS Vaccine Evaluation Unit in 1991. ¶

Will Morton