Sharon Riddler, MD, and, Madhu Choudhary, MD, have been awarded funding in the amount of $6,381,371 for a five-year grant by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) entitled “Native-like Envelope Trimer Therapeutic Vaccination for Induction of Broadly Neutralizing Antibodies to Facilitate HIV Functional Cure”. This proposal was submitted in response to the competitive funding opportunity entitled NIAID Clinical Trial Implementation Cooperative Agreement under funding opportunity number PAR-18-633.
Specific antibodies that block many strains of HIV are called broadly neutralizing antibodies or bnAbs. Rare people living with HIV (PLWH) develop these antibodies in their blood and others may have early or partially active antibodies. The purpose of this project is to conduct a clinical study of a new vaccine, called Trimer 4571, to determine if the vaccine is safe in PLWH and if it improves the antibody response to HIV. It is possible that individuals with chronic HIV-1 infection have elicited precursors of HIV bnAbs, but that these responses have been stunted by viral escape or by affinity maturation away from highly conserved epitopes. If HIV bnAb precursors have been elicited in these individuals as the preliminary data indicates, then such responses could be boosted by delivery of native-like HIV-1 envelope (Env) trimers.
Development of therapies that may induce bnAb in vivo would be a valuable advance for both HIV-1 treatment and prevention. Using multiple, state-of-the-art assays, the team will measure the effect of the immunogen on the size of the peripheral blood HIV-1 reservoir and potential sieving effect on the residual plasma viremia and cellular HIV Env RNA. Trimer induced virologic and immunological assessments will provide new insights into the conditions and the benefits of these neutralizing antibody responses toward achieving sustained remission of HIV in the absence of antiretroviral therapy.
Congratulations Sharon and Madhu!