Infectious disease researchers at the University of Rochester School of Medicine and Dentistry will use $3.1 million from the National Institutes of Health to find new ways to develop a vaccine to prevent HIV, the virus that causes AIDS.
Since the first HIV vaccine trial was conducted at the University of Rochester Medical Center in 1988 progress has been made, but the ultimate goal of creating a safe, effective and durable HIV vaccine remains elusive. When the NIH called for “innovative, high risk, high impact research to identify novel vaccine concepts” in a recent funding announcement, James J. Kobie, Ph.D. was ready with a unique strategy that hasn’t been tested before.
Most vaccines, like the flu vaccine, spur the body to produce T cells–immune cells that are poised and ready to attack when foreign invaders like viruses enter the body. T cells also help other immune cells respond to threats. HIV, which stands for human immunodeficiency virus, is unique because it directly infects these helper T cells. Stimulating the body to produce additional T cells could create more targets for the virus – exactly what researchers don’t want to do.
Kobie, an assistant professor in the Department of Medicine, Infectious Diseases, will test a vaccine approach with an in-depth focus on a different type of immune cell: B cells. Like T cells, B cells help the body eliminate foreign molecules, but in a different way: they produce antibodies, proteins that latch onto intruders, inhibit their ability to function and mark them for destruction.
Typically, B cells rely on T cells to help them make antibodies. Kobie thinks that prodding B cells to produce antibodies without T cell help will encourage the body to reject the virus while avoiding the creation of excessive T cells that the virus thrives on. The NIH awarded $2.7 million for this research, which will be led by Kobie and conducted by his laboratory in partnership with scientists from the Oregon Health and Science University.
"One original and innovative aspect of James’ study is his focus on a specific type of B cell, so-called IgM memory cells, which have been little studied to date, but may play a key role in facilitating immune protection at the tissue sites where HIV is commonly transmitted,” said Stephen Dewhurst, Ph.D., vice dean for research at the School of Medicine and Dentistry and chair of the Department of Microbiology and Immunology, whose lab also studies HIV vaccine development.
Kobie’s second NIH grant, for $400,000, will take advantage of research already underway at the University of Rochester’s HIV Vaccine Trials Network site, also known as the Rochester Victory Alliance. Under the leadership of Michael C. Keefer, M.D., the Victory Alliance conducts clinical trials of preventive HIV vaccines, enrolling healthy individuals from in and around Rochester.
Keefer’s team is currently conducting a trial of an experimental HIV vaccine and will measure antibodies against HIV in blood samples obtained from participants. Kobie will take this work a step further, testing HIV-specific antibodies in tissue from the mouth and rectum, where the HIV virus typically enters the body. With the help of Alexander Rosenberg, Ph.D., director of bioinformatics in the Department of Medicine, Kobie’s laboratory will analyze these samples to determine how various vaccines stimulate the production of protective antibodies at these entry points.
“Eliminating the virus where it first comes in contact with the body is critical to the development of an effective vaccine,” said Keefer, professor in the Department of Medicine, Infectious Diseases who has more than 20 years of experience in the preventive HIV vaccine field. “This research will help us understand, in greater detail than ever before, why some HIV vaccines are partially effective while others are not, and will allow us to identify strategies to include in the development of future HIV vaccines.”
Kobie credits the University of Rochester Center for AIDS Research and the Rochester Victory Alliance for these awards: both programs provided seed funding that allowed Kobie to test his ideas and gather the data needed to secure grants in today’s competitive funding environment.
“These projects bring together a very talented team of researchers and clinicians to understand how humans respond to HIV vaccines at their most vulnerable sites,” said Kobie. “I am very excited to translate the knowledge we obtain into new HIV vaccine strategies.”