Campbell Foundation Grant Funds UM Research Using Anti-Malaria Drugs to Enhance AAV-Based HIV Vaccines
FORT LAUDERDALE, FL –– April 26, 2023 – One of the greatest challenges in the development of a vaccine for HIV is the huge number of variants found in people around the world. This variation is due to the virus’ ability to rapidly mutate and evade the body’s own immune responses.
To address this large variation in HIV viruses, researchers have turned to broadly neutralizing antibodies capable of binding and neutralizing the majority of circulating HIV strains. The genetic sequence of broadly neutralizing antibodies is encoded into adeno-associated virus (AAV), a carrier virus frequently used for gene therapy, and inoculated into the muscle.
Following inoculation, the muscle cells will continue to make the broadly neutralizing antibodies long term, treating an ongoing HIV infection or protecting an individual from HIV acquisition.
While AAV-based vaccines for HIV have been shown to be effective, at times the body’s immune system recognizes the delivered antibodies as foreign and targets them for destruction.
The Campbell Foundation has awarded an $80,000 grant to James Termini, PhD., a research assistant professor at the University of Miami ,who is developing a way to keep the body’s immune system from recognizing antibodies as foreign by using known drug inhibitors of TLR9, (an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells) as a pre-treatment to AAV delivery.
“We propose to validate three anti-malarial drugs that are already approved for human treatment and are known to inhibit TLR9,” says Termini. “These drugs include Chloroquine, Quinacrine, and Hydroxychloroquine. In our preliminary studies, these three drugs have been shown to reduce TLR9 signaling by more than 80% in cell lines.”
The hope is that researchers will see more consistent delivery as well as less immune recognition and clearance of the delivered antibodies. Currently, the immune recognition of AAV-delivered antibodies is the one major limitation to this technology.
“This could represent a functional cure for HIV. With a single inoculation an individual could be protected for life and not have to be on a cocktail of medications that often cause other side effects,” says Campbell Foundation Executive Director Ken Rapkin.
Termini’s hope is to revolutionize the field of recombinant AAV delivery of bNAbs and find a functional cure for HIV.
“If the technology and the immunosuppressive approach work as anticipated by the investigators, it may be applicable to other vector-based therapies. This appears to be a high risk/high reward project, and I think it matches the goals of The Campbell Foundation to support HIV research, often as a catalyst to help people addressing a relevant question and potentially establishing a larger project,” said one Campbell Foundation peer review member.
About The Campbell Foundation
The Campbell Foundation was established in 1995 by the late Richard Campbell Zahn as a private, independent, nonprofit foundation dedicated to supporting clinical, laboratory-based research into the prevention and treatment of HIV/AIDS. It focuses its funding on supporting alternative, nontraditional avenues of research. The Campbell Foundation has given away more than $12 million since its inception.