Project Summary: The global epidemic of HIV continues to pose a major world health threat with more than 1.5 million new infections diagnosed in 2021. Although significant efforts have been underway for more than 30 years to develop a vaccine to prevent HIV infection, to date, only one trial has shown any significant efficacy at infection prevention. A recent study showed that monocyte gene enrichment correlated with the antibody dependent Fc effector functions thought to be the reason for this vaccine’s efficacy. Monocytes are highly versatile cells that regulate immune response through direct and indirect ways through secretion of cytokines. Monocytes are recognized for their ability to contribute to vaccine efficacy across multiple vaccines, including malaria, influenza and BCG. We hypothesize that monocyte subpopulations play a critical role in regulating development HIV vaccine elicited antibody response through innate help and that, once characterized, can be harnessed to improve vaccine efficacy. We will investigate this by two aims. Aim 1 will evaluate changes in monocyte gene expression following infection, auto-immune disease and vaccination using publicly available data and validate in healthy subjects an. Aim 2 will specifically identify monocyte sub-type specific signatures associated with antibody response after HIV vaccination from four recent HVTN trials using CITE-seq and a novel discrete-state mathematical algorithm with in vitro validation. Dr. Keefer and Dr. Thakar are the ideal mentors for this project given their expertise in HIV vaccine research and systems biology. Through this project, I will develop my computational and translational research and build a foundation from which I can transition to independence as a physician scientist.