Bradley Receives NIH Grant to Study Natural Killer Cell Regulation of the Germinal Center HIV Neutralizing Antibody Response
Todd Bradley, PhD, Center for Pediatric Genome Medicine, is the principal investigator on a $725,421 R56 grant from the National Institutes of Health (NIH).
Dr. Bradley’s study, “Natural Killer Cell Regulation of the Germinal Center HIV Neutralizing Antibody Response” aims to determine key molecular pathways that are critical for natural killer (NK) cell immunoregulation of the HIV antibody response that can be targeted during future vaccine strategies to improve elicitation of protective HIV antibodies.
“Generating protective antibodies called broadly neutralizing antibodies (bnAbs) that can neutralize the diversity of circulating HIV viruses to protect against infection has not occurred with any current vaccines, but do occur in about half of people infected with HIV,” Dr. Bradley explained. “By analyzing the immune cells of HIV infected individuals who developed bnAbs we found that they have increased frequencies of dysfunctional natural killer cells that correlated with the development of bnAbs.” Dr. Bradley Said. “Natural killer cells are fast acting immune cells that recognize and kill tumors and viruses, but we showed they also could kill T cells that provide help to antibody producing cells, identifying NK cells as potential regulators of antibody responses. However, the specific cell receptors and molecular mechanisms important for this regulation are unknown.”
This project is a continuation of a preliminary study the team performed in monkeys to address the effects of transient NK cell depletion on the response to HIV Envelope vaccination.
“Identifying the molecular mechanisms and receptor-ligand interactions that mediate NK cell inhibition of the HIV antibody response will identify novel NK cell-targeting strategies that can be applied during HIV-1 vaccination to improve immune responses,” Dr. Bradley said.
Children’s Mercy Kansas City is an independent, non-profit, 386-bed pediatric health system, providing over half a million patient encounters each year for children from across the country. Children’s Mercy is ranked by U.S. News & World Report in nine specialties. We have received Magnet® recognition five times for excellence in nursing services. In affiliation with the University of Missouri-Kansas City, our faculty of more than 800 pediatric specialists and researchers is actively involved in clinical care, pediatric research and educating the next generation of pediatricians and pediatric subspecialists. The Children’s Mercy Research Institute (CMRI) integrates research and clinical care with nationally recognized expertise in genomic medicine, precision therapeutics, population health and health care innovation. In 2021 the CMRI moved into a nine-story, 375,000-square-foot space emphasizing a translational approach to research in which clinicians and researchers work together to accelerate the pace of discovery that enhances care.