September 24, 2009

WORCESTER, Mass. – The University of Massachusetts Medical School (UMMS) has received funding for two, five-year grants from the National Institute of Allergy and Infectious Diseases (NIAID) totaling $18 million to pursue research and development of a vaccine designed to prevent infection with human immunodeficiency virus (HIV), the virus that causes AIDS. Shan Lu, MD, PhD, professor of medicine and biochemistry and molecular pharmacology whose work has focused on novel vaccine development, will be the lead investigator on both projects. The projects build on earlier investigations into the induction of protective antibody responses against human HIV.

“Finding an effective preventive AIDS vaccine will help break the transmission cycle of HIV in the world and offers hope for the millions of people suffering from this deadly disease,” said Dr. Lu.

One of the worst pandemic diseases in modern times, approximately 1.2 million people in the United States and more than 30 million people worldwide live with HIV (UNAIDS 2008). HIV attacks vital cells in the human immune system causing it to weaken and fail. As a result, patients with the virus develop AIDS and are susceptible to life-threatening opportunistic infections associated with the progressive failure of the immune system.

Currently, there is no vaccine available to prevent HIV infection. Anti-retroviral therapy can control progression to AIDS but cannot cure or stop the spread of the disease, and for every individual that begins treatment about three more become infected. Historically, vaccines have significantly impacted the spread of infectious diseases such as smallpox, polio, measles, and yellow fever. Similarly, HIV vaccines represent the best long-term hope for ending the HIV pandemic, and HIV vaccine research is a top priority for NIAID.

The project, “Induction of neutralizing antibodies targeting CD4-binding region of HIV-1 Env,” funded through a $10 million grant from NIAID’s HIV Vaccine Research and Design grant program, will explore the development of protective antibodies targeting the area of the virus that binds to human immune cells – a vulnerable spot of the virus. Lu and his team, which includes Paul Clapham, PhD, associate professor of molecular medicine at UMMS, Shiu-Lok Hu, PhD, professor of microbiology and pharmaceutics at the University of Washington, and Xiangpeng Kong, PhD, associate professor at NYU Langone Medical Center, will analyze how HIV can use different mechanisms to enter host cells, as well as how the structural changes on receptor binding areas may impact the development of novel vaccines.

Eliciting protective antibodies has, thus far, been a serious challenge for scientists, according to Lu. “Working with colleagues at UMass Medical School, the University of Washington and NYU Langone Medical Center, we hope to uncover new biological insights into the production of promising HIV vaccine candidates by targeting the most vulnerable part of the virus,” he said.

The second project, “Optimization of HIV vaccine for the induction of cross-reactive antibodies,” an $8 million grant funded under NIAID’s Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) grant program, will research the use of a “cocktail” of multiple viral antigens to develop the next generation of HIV vaccine formulations. Recently tested in a Phase I clinical trial at UMMS, this approach was found to be effective in producing promising immune responses against HIV antigens in healthy volunteers. Dr. Lu’s team and colleagues at Advanced BioScience Laboratories (ABL), a Maryland biotech company, will test the new formulation’s ability to safely produce better protective immune responses in patients. Working with Dr. Lu is Egil Lien, PhD, assistant professor of infectious disease and Gary Ostroff, PhD, research professor of molecular medicine at UMMS and Phil Markham, PhD, scientific director at ABL.

“Both studies will produce valuable insight and knowledge into the development of vaccines against HIV as well as other emerging infectious diseases,” said Lu. “UMass Medical School has developed a leading research program in immunology, infectious diseases and vaccine. These grants are the result of this long-term investment in a highly competitive area.”

About the University of Massachusetts Medical School
The University of Massachusetts Medical School has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $200 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit