UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL BEGINS  CLINICAL TRIAL FOR HIV VACCINE

March 22, 2004

WORCESTER, Mass.— After years of intense research and testing, a new vaccine for human immunodeficiency virus (HIV), developed by scientists at the University of Massachusetts Medical School (UMMS)  and Advanced BioScience Laboratories, Inc. (ABL),and funded by the National Institute of Allergy and Infectious Diseases (NIAID), has been designated as an investigational new drug (IND) by the U.S. Food and Drug Administration.  The FDA has also given UMMS the green light to begin a clinical trial to test the vaccine’s safety and immunogenicity in people.

“This is a landmark development and a major step forward in HIV vaccine research,” said Shan Lu, MD, PhD, associate professor of medicine and head of the HIV vaccine effort at UMMS. “Our vaccine is based on elements from primary virus isolates drawn from all over the world, and that, I think, will make a difference in the efficacy of the vaccine.”

Dr. Phillip Markham, Director of Cell Biology and principal investigator of the  ABL/UMMS HIV Vaccine Design and Development contract team, agrees that this is a very promising vaccine approach that should address certain shortcomings observed in previous trials.

HIV, the virus that leads to acquired immune deficiency syndrome (AIDS), remains a global epidemic. World health officials estimate 42 million people are now infected with HIV. Some three million people worldwide died of AIDS last year, and millions more are expected to die from AIDS this year. With the rate of infection accelerating in many parts of the world, the search for an effective HIV vaccine is one of the highest public health priorities. Yet, development of an HIV vaccine has been challenging because of the virus’ extraordinary degree of genetic diversity. HIV mutates rapidly in the environment making it an elusive target for traditional vaccine strategies.  That’s where UMMS and ABL have made significant progress.  They have created a novel “polyvalent” HIV vaccine based on multiple strains of HIV collected directly from infected people living in five locations around the globe, representing five different strains of the virus.  “Instead of hitting HIV with one target, we are using five in this vaccine,” Dr. Lu said. “The goal with this vaccine is to trigger the immune system to target multiple strains of the virus.”

The approach developed at the Medical School uses elements of HIV’s DNA to induce an immune response to the virus. The DNA is then boosted by an injection of recombinant viral proteins developed by ABL that have been shown to enhance the host’s immune response to the DNA elements of the vaccine in animal models. So far, the DNA and protein combination has been tested in two animal models with very promising results. Antibodies produced by the immunized animals effectively neutralized live HIV isolates collected from several parts of the world.   That success facilitated taking the novel vaccine to the next step, a clinical trial in humans.   “There is no live HIV in the vaccine, only elements from the DNA that code for the envelope and gag proteins of the virus, so there is no chance of getting HIV from this vaccine,” Dr. Lu said.

The clinical trial will be directed by Jeff Kennedy, MD, assistant professor of medicine at UMMS who works in the school’s Center for Infectious Disease and Vaccine Research. The trial will enroll 36 people who do not have HIV. They will be given the DNA and protein boost vaccine, and then their immune responses will be measured over time. “The results in the animal models have been very encouraging and we are now ready to determine whether the vaccine can produce significant immune responses in people,” Dr. Kennedy said.

The clinical trial is expected to last about 18 months. (Each participant will be involved for only 12 months, but because recruitment will take place over time, the length of the overall trial will run beyond one year.) Over the course of the trial, each participant will receive three doses of the DNA element of the vaccine and two doses of the protein boost element of the vaccine. The participants will be monitored at regular intervals and researchers will look for both antibody responses and cell-mediated responses, which is the ability of the vaccine to cause people to produce T-cells that hunt down and kill HIV-infected cells. “Antibodies are like the infantry, moving through the bloodstream and attacking what virus they find. The T-cells are like the special forces, with a specific mission to seek out and destroy the virus where it hides,” Dr. Kennedy said.

Recruitment for the trial is focused on enrolling participants who live within an hour’s drive of UMMS in Worcester. People who are in reasonably good health and interested in finding out more about participating in the trial should call 888-687-5757. Or, they can log on to  www.umassmed.edu/cidvr/clinical_trials/vaccine and leave contact information on that secure, confidential site. “I’m always impressed with people who volunteer for clinical trials,” Kennedy said. “They are pioneers, doing something very important for medical research and mankind.”

To look for the immune responses, Dr. Kennedy’s team will sample the participants’ blood and test sera and blood cells at the bench for immunity against HIV and HIV- infected cells. The hope is that the human sera will neutralize HIV and immune cells will attack HIV-infected cells, indicating the vaccine would be protective against the virus in the general population.  “In the animal models, the vaccine was able to neutralize the live HIV, but the human immune system is far different,” Dr. Kennedy said. “So we’ll have to wait and see how this very promising vaccine actually performs in people.”

Both the vaccine research and the clinical trial are funded by an NIAID contract awarded in 2000 under an HIV Vaccine Design and Development Team (HVDDT) program to ABL and the UMMS.

The award was part of a $70 million commitment by the NIH that year to just four public-private partnerships worldwide in an effort to accelerate the development and testing of promising HIV vaccines. In addition to the UMMS/ABL partnership, HVDDT contracts were also awarded to the Chiron Corporation of Emeryville, California; the University of New South Wales, Australia; and Wyeth Lederie Vaccines and Nutrition of Pearl River, New York, in collaboration with the University of Pennsylvania and Duke University.

The University of Massachusetts Medical School, one of the fastest growing medical schools in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. UMass Medical School and its clinical partner, UMass Memorial Health Care, attract more than $151 million in research funding annually, 80 percent of which comes from federal funding sources. Research funding enables the researchers to explore human disease from the molecular level to large-scale clinical trials.

Advanced BioScience Laboratories, Inc. (ABL), located in Kensington, Maryland, is a biomedical research, development and manufacturing company focusing on human retroviral diseases.  ABL has been a leader in HIV-1 research for more than two decades and has been involved in the development of methods to both prevent and treat HIV-1 infection.

Under a licensing agreement, CytRx Corporationof Los Angeles will assume responsibility for the commercializing of the HIV vaccine and ownership of the FDA registration.

Contact: Michael Cohen  508-856-2000    michael.cohen@umassmed.edu