PRELIMINARY RESULTS FROM HIV VACCINE TRIAL SHOW PROMISE 

Novel vaccine generates T-cells and antibodies to HIV. More testing needed to plan next steps for vaccine development program. 

September 7, 2005 

WORCESTER, Mass. - Preliminary results from a phase 1 clinical trial of 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), show the vaccine's ability to generate antibody and T-cell responses in otherwise healthy people not infected with HIV.

The preliminary results were presented September 7, 2005 at the AIDS Vaccine 2005 International Conference in Montréal, Canada, by  Jeff Kennedy, MD,  assistant professor of medicine and member of the UMMS Center for Infectious Disease and Vaccine Research, who lead the clinical trial. "We're still a long way from having a vaccine against HIV, but the results of this trial are scientifically important and encouraging," Dr. Kennedy said. "To my knowledge, this is the first report of an HIV vaccine generating antibodies in healthy people that can neutralize several strains of the virus."

Under a licensing agreement,  CytRx Corporation of Los Angeles has the rights to commercialize the HIV vaccine formulation tested in this trial including more advanced phases of human studies.

HIV, the virus that leads to acquired immune deficiency syndrome or AIDS, remains a global epidemic with world health officials estimating 42 million people now infected with the virus. Development of an HIV vaccine has proven challenging, however, given the virus' extraordinary ability to mutate, making it an elusive target for traditional vaccine strategies. 

The HIV vaccine tested at UMMS attempts to overcome the mutation problem by incorporating DNA elements from multiple strains of HIV collected directly from infected people living in five locations worldwide. The approach uses elements of HIV's DNA that code for the envelope protein (Env), which forms the outer coat of the virus. The vaccine's DNA elements enter the subjects' cells and express Env antigens, which make the body think those cells are infected with the AIDS virus. The subjects then receive doses of viral proteins that are designed to enhance the host's immune response to the Env antigens.  "I am very encouraged by these results. It is proof-of-principle data that the concept of a DNA prime and protein boost approach can induce strong antibody responses," said  Shan Lu, MD, PhD , associate professor of medicine and head of the HIV vaccine development efforts at UMMS. "We must now continue our work to analyze the data from this trial and to plan our next steps to refine and improve this HIV vaccine's formulation."

The phase 1 trial was designed to test the safety of the vaccine and to monitor the vaccines' ability to generate immune responses to HIV in people who had never been exposed to the virus. The trial, conducted at the UMMS campus in Worcester, began on April 12, 2004.  Over the course of some 12 months, a total of 34 healthy volunteers were eventually enrolled-23 men, 11 women. The first injection of the vaccine occurred on April 26, 2004.  Over the course of several weeks, each participant received three doses of the DNA element of the vaccine and two doses of the protein element. The participants were divided into three groups: Group A received the DNA vaccine intradermaly, while Groups B and C received the DNA vaccine intramuscularly, with Group C volunteers receiving a six-fold higher DNA dose.  All participants received the same amount of protein "boost" via two intramuscular injections.The final injection of the trial occurred on April 12, 2005. All participants were monitored at regular intervals with blood samples drawn at several times over 12 months.

Blood was analyzed for two kinds of responses: antibody responses and cell-mediated responses or the ability of the vaccine to induce 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.

While analysis of the serum from the volunteers is ongoing, Dr. Kennedy reported that tests to date show the vaccine did induce measurable T-cell responses and antibody responses to multiple strains of HIV.  The antibodies from the participants' sera were sent to Duke University and tested against HIV in cultures. Those tests showed the antibodies produced by many of the volunteers were able to neutralize multiple strains of HIV. The level of neutralizing ability varied significantly, both from person to person and in relation to the various strains tested.  Some samples had more significant neutralizing ability than the others. "As HIV is a highly mutating viral disease, the ability for one vaccine to neutralize multiple clades (strains) of the virus simultaneously could be essential. That problem has been considered among the primary challenges to successful HIV vaccine development, so we're encouraged by the results we're seeing," Dr. Kennedy said. 

On the question of vaccine safety and tolerability, Dr. Kennedy reported that the vaccine was generally well-tolerated.  Many of the subjects in the trial did have some rash-like skin reactions at the site of injections. Those reactions, which are not uncommon for many vaccines in use today, cleared up without treatment.  In one person, however, a participant in Group C of the trial, a type of skin reaction called leukocytoclastic vasculitis (LCV) was observed.  The LCV reaction included rashes on several parts of the body not associated with the point of injection. The LCV case resolved on its own, without the need for treatment.  LCV is a known side-effect of several approved vaccines, including influenza, tetanus, pertussis and measles. It is also a documented side-effect for numerous medications in routine human use.  Nevertheless, Dr. Kennedy and the members of the trial's safety committee decided to stop additional injections for the remaining participants in Group C.  By then, the majority of the volunteers had received
the full course of vaccine and sufficient scientific information should be produced from
the samples collected from this study. 

Going forward, Dr. Kennedy said his lab will continue to analyze the sera samples from the volunteers to better characterize the T-cell responses and will present all the data in the coming year. Meanwhile, Dr. Lu said there is more work to be done analyzing the mechanisms of the vaccine formulation in hopes of improving its ability to generate an immune response that could be protective.  "We look forward to working with colleagues in the HIV vaccine field to better understand these results and to move forward with the novel approach we have tested in this trial," Dr. Lu said.

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 UMMS. 
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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 $174 million in research funding annually, 80 percent of which comes from federal funding sources.
 
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.

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