Immune Therapy and Modulation

Our very dynamic research program addresses infectious diseases treatment through modulation of the host immune response. Under investigation are immune therapies that treat HIV, HCV, influenza, malaria, and tuberculosis (TB). The immune therapy program for treating HIV infection includes therapeutic vaccinations, targeting the PD-1 inhibitory pathway and various combinations of these two approaches. Dr. Rama Amara’s laboratory spearheads these studies in collaboration with Dr. Rafi Ahmed’s laboratory at Emory University and Dr. Gordon Freeman’s laboratory at Harvard University. The principle research goal is to restore and enhance the function of anti-HIV immunity of the infected individual by blocking the inhibitory receptors on immune cells and by generating immune cells that can efficiently fight HIV infection. Therapeutic vaccination and PD-1 blockade approaches have shown highly encouraging results for controlling pathogenic SIV infections in the non-human primate model. The Emory Vaccine Center holds the distinction of testing the first generation therapeutic vaccine for HIV-infected humans in the United States. Additional immune therapy approaches investigate ways to purge the viral reservoirs in HIV-infected and drug-treated individuals so as to achieve a functional cure for HIV.

Drs. Guido Silvestri and Mirko Paiardini laboratories study the mechanisms by which HIV is able to cause immune dysfunction and accelerate disease progression. Information gained from these studies will be critical to the development of novel immune therapies to treat HIV infection. EVC scientists are examining the PD-1 blockade approach as a potential target for purging the virus from latently infected cells and for treating chronic HCV infection and certain cancers. Current testing in humans revealed encouraging safety and efficacy results.

Great interest surrounds Drs. Rafi Ahmed’s and Jens Wrammert’s identification of new monoclonal antibodies that have a broad cross reactivity to multiple flu serotypes. These antibodies have been shown to treat a lethal flu infection even when administered 1-3 days after infection.

Vaccines

HIV/AIDS: Developing vaccines to halt the AIDS epidemic are central to the mission of the Emory Vaccine Center.  The AIDS vaccine program is comprehensive, spanning the entire research process from basic science to translational research and through preclinical and clinical trials. Rama Amara, focuses on preventive vaccines for HIV/AIDS that use the DNA and MVA vectors in NHP. A DNA/MVA HIV vaccine, developed by Dr. Amara and EVC faculty member Dr. Harriet Robinson (currently at Geovax.), generated a strong anti-HIV cellular and humeral immunity. The human Phase IIa trial (HVTN 205) is complete. Building upon these studies, Dr. Amara developed GM-CSF (in collaboration with Dr. Robinson) or CD40L-adjuvanted DNA/MVA vaccines. Results showed that these vaccines prevent 60-70% of the vaccinated rhesus macaques from a repeat heterologous mucosal SIV infection. Based on this excellent protection outcome, Geovax has begun a Phase I safety study using the GM-CSF-adjuvanted DNA/MVA vaccine in humans through HIV Vaccine Trials Network (HVTN)/NIH. Plans are underway to test the CD40L-adjuvanted DNA/MVA vaccine in humans.

Dr. Amara, in collaboration with Dr. June Scott, also is working on the use of a probiotic bacterium Lactococcus lactis expressing HIV immunogens as an oral vaccine for HIV. It is designed to prevent infection by blocking infection at the site of virus exposure. Preliminary results in mice demonstrated that this vaccine generates a strong anti-HIV immunity at the mucosal sites where HIV can potentially enter into the body. Dr. Amara has initiated a pilot macaque study investigating the vaccine in an animal model to provide the basis for future study of its protective efficacy against HIV.

In addition, Dr. Amara is working with Dr. Shahid Jameel at the International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India to develop a CD40L-adjuvanted DNA/MVA vaccine for subtype C strain of HIV (a prevalent strain in India).