With $42 million in funding from the National Institutes of Health, scientists from Beth Israel Deaconess Medical Center (BIDMC) and Oregon Health &Science University (OHSU) will lead a five-year research initiative to advance efforts to cure and prevent HIV/AIDS. Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC, and Louis Picker, MD, Assistant Director of the OHSU Vaccine and Gene Therapy Institute, will lead a consortium of researchers from across the country exploring the mechanisms behind promising new HIV vaccine candidates and potential cure strategies.
More than 35 million people worldwide are infected with HIV, and more than 2 million new infections develop each year. "Antiretroviral therapies have allowed people infected with HIV to lead longer, healthier lives, but a vaccine and a definitive cure for infection would accelerate an end to this global epidemic," said Barouch, who is also Professor of Medicine at Harvard Medical School.
The researchers will focus their work in two key areas: 1) understanding the mechanisms of why the current preventive HIV vaccines developed by Barouch and Picker are providing protection from infection in nonhuman primates; and 2) building on that knowledge to create both an effective preventive and therapeutic (cure) HIV vaccine.
"This grant gives us the opportunity to more closely collaborate with other scientists around the country who have a common goal: to end the HIV epidemic," said Picker, who is also a Professor of Pathology/Molecular Microbiology and Immunology in the OHSU School of Medicine. "Stopping HIV may require a combination of vaccine approaches to get to full protection. There are just a handful of promising vaccine platforms out there, and if we can better understand why they are working, we'll have a better shot at getting to the next generation of therapeutic vaccines that could cure current HIV infections."
Barouch will lead a group of scientists from BIDMC and other institutions to define how candidate HIV vaccines may be able to protect against infection. They will study an adenovirus serotype 26 vectored vaccine with a purified HIV envelope protein (the surface protein of the HIV virus), which enhances the immune responses. This vaccine candidate was developed by Barouch and colleagues at BIDMC and is currently in international Phase 2a clinical trials.
In 2015, Barouch was lead author on a study in Science showing that a novel HIV vaccine using adenovirus serotype 26 (Ad26) regimen he and his research team developed at BIDMC provides robust protection against the virus in non-human primates. The study results showed that in half of the vaccinated non-human primates the prime-boost vaccine regimen provided complete protection against a series of six repeated challenges with the simian immunodeficiency virus (SIV), a virus similar to HIV that occurs in nonhuman primates.
With this new federal funding, Barouch and colleagues will evaluate the types and functions of the antibodies and cell-mediated immune responses induced by this vaccine, which will lead to a deeper understanding of how this vaccine might be able to protect HIV-uninfected individuals and also whether this vaccine could be used in HIV-infected individuals to help control the virus in the long term.
"With this vaccine candidate already in Phase 2a clinical trials, the knowledge gained in this research program will be immediately applicable to the development of clinical interventions," Barouch said.
Concurrently, Picker will lead a team of investigators from OHSU working to better understand the efficacy of their unique preventive vaccine that uses cytomegalovirus (CMV) as the vector and is heading to Phase 1 human clinical trials next year in Portland, Ore. Picker's 2013 landmark discovery published in Nature showed in nonhuman primates that OHSU's preventive vaccine not only controlled and stopped SIV, the nonhuman primate form of HIV, from spreading, but also cleared the virus in 50% of the primates' systems.
"What we know so far is that our preventive vaccine using the unique CMV vector is able to control and clear the virus in nonhuman primates, but we haven't shown why it works. Once we have a better understanding of the mechanisms that are making the preventive vaccine effective, there's a chance that we could also optimize our vaccine, along with others," said Picker.
In addition to Barouch and Picker, grant funding from the National Institute of Allergy and Infectious Diseases (UM1 AI124377), part of the NIH, will also support the work of Galit Alter, PhD, Ragon Institute of MGH, MIT and Harvard; R. Paul Johnson, MD, Emory University; Dennis Burton, PhD, Scripps Research Institute; Jeff Lifson, MD, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research;Rafick Sekaly, PhD, Case Western Reserve University; and Wenjun Li, PhD, University of Massachusetts Medical School.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.