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Experimental Trial Combines DNA Vaccine With Triple-Drug Therapy To Stop HIV

Date:
January 26, 1998
Source:
University Of Pennsylvania Medical Center
Summary:
In a new clinical trial, researchers at the University of Pennsylvania Medical Center are combining a proven antiretroviral drug therapy with an experimental DNA vaccine in an effort to eradicate HIV in infected patients.

In a new clinical trial announced Jan. 23, researchers at the University of Pennsylvania Medical Center are combining a proven antiretroviral drug therapy with an experimental DNA vaccine in an effort to eradicate HIV in infected patients.

The drug regimen, in which three different agents that block HIV replication are given concurrently, has been shown to lower levels of the virus in many patients to levels undetectable by all but the most sensitive assays. Immune system function is often restored in individuals receiving this therapy, returning them to health. They cannot be considered cured, however, because the virus lingers quiescently in certain subpopulations of T cells.

The experimental vaccine incorporates elements from four HIV genes -- env, rev, gag, and pol -- and is the most advanced version of a new DNA immunization technology that has demonstrated the ability to spark a range of immune system responses in previous animal and human trials. In a trial conducted last year with HIV-positive patients, for example, a vaccine containing only the env and rev genetic constructs triggered a statistically significant rise in antibodies, but did not appear to alter the course of the infection.

The hope in the current trial is that, in HIV-positive patients whose virus levels have been lowered by drug therapy to allow their immune systems to rebound, the vaccine will boost immune activity sufficiently to clear the virus from their bodies.

"We think we can get an enhanced response to the DNA vaccine in conditions where the immune system is not preoccupied simply with maintaining itself against an HIV infection," explains Rob Roy MacGregor, MD, a professor of medicine and director of AIDS clinical trials at the Hospital of the University of Pennsylvania. MacGregor is principal investigator on the trial. "Also, we're using a broader-based, possibly more effective vaccine than in our earlier study, one that contains genetic material from four different HIV genes instead of only two."

"We're trying to train all of our guns on HIV," says David B. Weiner, PhD, developer of the new DNA vaccine technology and an associate professor of pathology and laboratory medicine. "So, we're suppressing the virus in patients with triple-drug therapy, which doesn't cure them but dramatically lowers their viral load, allowing them perhaps to mount a more robust immune response. Then we're giving them the improved vaccine."

Immunologically, the concept of a therapeutic DNA vaccine for a viral infection poses something of a conundrum. How can a vaccine strategy based on producing antigenic gene products from parts of four of HIV's nine genes raise any additional immune response beyond that engendered by the naturally occurring gene products from the nine full genes active in the ongoing infection?

"Historically, the most powerful immune response results from a natural infection," notes MacGregor. "A case of chicken pox gives you better immunity than the chicken pox vaccine, for example. So, it was counterintuitive to me in our earlier DNA vaccine trial with HIV-positive patients that there would be an increased immune response over that produced by the virus already circulating in the body. In that trial, however, we saw a statistically significant, measurable rise in antibodies against the virus."

MacGregor hypothesizes that the added immune response may result from differences in the way the antigens are presented to the immune system by the vaccine. With the vaccine, viral DNA is introduced into muscle cells, which then produce HIV gene products, and muscle cells are not normally involved in an HIV infection.

According to the protocol for the new trial, 21 patients in three groups of seven will be given escalating doses of the two parts of the vaccine over the next few months. Each group's vaccine dose will be approximately three times the previous group's dose level. This procedure maximizes the opportunity to see positive immunological results while minimizing the possibility of adverse reactions in the study participants and is in keeping with the purpose of the Phase I trial, which is to demonstrate the safety of the new combination of drug therapy and DNA vaccination.

Support for the clinical trial is provided by the National Institutes of Health, and the experimental vaccine for the trial is manufactured by Apollon Inc., a biotechnology firm located in Malvern, Pennsylvania.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation -- $149 million in federal fiscal year 1996. In addition, for the second consecutive year, the institution posted the highest growth rate in its research activity -- 9.1 percent -- of the top ten U.S. academic medical centers during the same period.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Experimental Trial Combines DNA Vaccine With Triple-Drug Therapy To Stop HIV." ScienceDaily. ScienceDaily, 26 January 1998. <www.sciencedaily.com/releases/1998/01/980126060936.htm>.
University Of Pennsylvania Medical Center. (1998, January 26). Experimental Trial Combines DNA Vaccine With Triple-Drug Therapy To Stop HIV. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/1998/01/980126060936.htm
University Of Pennsylvania Medical Center. "Experimental Trial Combines DNA Vaccine With Triple-Drug Therapy To Stop HIV." ScienceDaily. www.sciencedaily.com/releases/1998/01/980126060936.htm (accessed July 31, 2014).

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