HIV/AIDS Research at Emory
HIV virions. Image courtesy CDC.
The HIV vaccine research field has been marked by cycles of hope and disappointment. HIV has presented a unique challenge to vaccine design because it mutates so quickly and because it infects cells that play a central role in regulating the immune system. To meet these challenges, Emory’s HIV vaccine efforts draw upon basic immunology, translational research in non-human primates, investigations of how viral transmission takes place, and clinical trials testing promising vaccine candidates.
Emory University's Center for AIDS Research includes more than 100 investigators working on basic, clinical, translational and behavioral projects, including vaccine research. Emory’s clinical researchers benefit greatly from collaboration with one of the largest outpatient HIV treatment facilities in the country, which is staffed and directed by Emory School of Medicine faculty/physicians: Grady Health System's Infectious Disease Program, located at the Ponce Center in Midtown Atlanta. Emory’s Hope Clinic in nearby Decatur also is a focal point for HIV/AIDS clinical trials, education and outreach, in partnership with community organizations in the Atlanta region.
HIV/AIDS vaccine research is a primary focus of scientists at the Emory Vaccine Center and Yerkes National Primate Research Center. The Vaccine Center is one of the largest groups of academic vaccine scientists in the world, and combined with the extensive resources at Yerkes make Emory an academic research leader in the quest for an effective HIV vaccine.
DNA/MVA vaccine candidate
At the Emory Vaccine Center, Harriet Robinson, PhD, and her team developed a candidate "DNA/MVA" vaccine against HIV, based on immunization with DNA encoding HIV proteins followed by a modified vaccinia virus boost. Initially reported as effective in rhesus macaques in Science in 2001, the vaccine candidate has been licensed and is now being tested through GeoVax, Inc., a company initially launched by Emory University. The GeoVax candidate vaccine is in Phase II human clinical trials. Robinson left Emory and became GeoVax’s chief scientific officer in 2008. The same vaccine is being tested in a clinical trial as a therapeutic boost for the immune system in individuals already infected by HIV and undergoing antiretroviral treatment.
Non-human primate research
Experiments performed at Emory’s Yerkes National Primate Research Center have been critical for testing the DNA/MVA vaccine, illustrating the value of the simian immunodeficiency (SIV) virus model in rhesus macaques. In addition, work by investigators such as Guido Silvestri, MD, studying sooty mangabeys could reveal how some primates survive infection by SIV without having their immune systems crippled, as well as how HIV may have migrated from non-human primates to humans.
Through the study of chronic viral infections, Rafi Ahmed, PhD, Rama Rao Amara, PhD, and their colleagues have gained insight into how HIV tricks T cells into falling asleep, and how therapies targeted to certain immunoregulatory molecules might be able to reinvigorate them. Amara also has been investigating adjuvants, additives to a vaccine that could stimulate the immune system into mobilizing its defenses against HIV.
Bali Pulendran, PhD, and his colleagues are taking a systems biology approach, identifying parts of the innate immune system important for effective responses to vaccines, and using that information to design potent adjuvants. Researchers in the recently established Center for Systems Immunology are working to identify gene expression signatures that predict immunity to a variety of vaccines without exposing individuals to infection.
By working with public health researchers in Zambia and Uganda, Susan Allen, MD/MPH, Eric Hunter, PhD, and Cynthia Derdeyn, PhD have been studying discordant couples where one partner is infected and the other may become infected. This research allows them to analyze how HIV mutates to evade the immune system and how the body’s mucosal barriers constrain the spectrum of viruses that initiate infection.
Emory has worked closely with the Georgia Research Alliance to recruit top vaccine researchers, including GRA Eminent Scholars Ahmed, Hunter and Silvestri. Emory’s HIV vaccine research has benefited from proximity to antiretroviral drug discovery efforts, headed by Dennis Liotta, PhD, and Raymond Schinazi, PhD, and behavioral health and prevention research at Rollins School of Public Health.
The Emory Vaccine Center and the International Centre for Genetic Engineering and Biotechnology, were recently awarded an NIH grant to develop vaccines against HIV subtype C, the predominant strain circulating in India and several other countries. Based in New Delhi, the Vaccine Center and ICGEB in 2008 formed a joint venture to drive vaccine development and testing.
The Hope Clinic, led by Mark Mulligan, MD, is an integral part of Emory’s vaccine research program. Work with community groups in the Atlanta region has facilitated and enriched the Hope Clinic’s research on HIV vaccines. In cooperation with the HIV Prevention Trials Network and the HIV Vaccine Trials Network, Carlos Del Rio, MD has served as the principal investigator for several clinical trials. In addition, Emory has participated in several several industry-sponsored HIV vaccine studies under his leadership.