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.