The impact of B cell phenotypes in HIV infection on antibody responses.

In this project I am interested in the role of B cells in HIV infection, particularly in understanding how B cells function and phenotypes impacts antibody responses. As HIV infection directly targets the immune system, it is known that B cell function is disrupted and serum antibody responses can be inferior. I want to understand how this state of chronic infection impacts B cells and antibody responses to vaccination challenges or other natural infections. My question is three-fold: first, are B cells responding in HIV+ individuals acting in a functionally different manner? Second, do these B cells have a different phenotype? Finally, I want to know if these responding B cells encode less functional antibodies. To answer these questions I will be using blood samples from two cohorts: one from HIV+ individuals who have had COVID-19 and one from HIV+ individuals following seasonal influenza vaccination, for each cohort I will be comparing them to healthy controls.
I will be assessing differences in serum titres against different viral antigens in our cohorts and healthy using ELISAs and neutralization-based assays. To investigate the differences in phenotypes I will use a flow cytometry-based approach to assess changes in naïve and memory B cell phenotypes post-vaccination or post-COVID-19. We expect to see differences both in phenotype and functions between HIV+ individuals post-vaccination or post-COVID-19 compared to healthy controls, we hope to correlate these observations to available clinical data. Finally, we will use single-cell sorting to study the functionality of produced antibodies.
This project will give us a novel understanding of how in chronic HIV infection B cells function and phenotype is modulated, and how this impacts the quality of the antibody response produced when challenged with immunization or other infection. This is of particular interest as the HIV+ population is slowly aging and thus will develop a weaker immune system leading to becoming more sensitive to other pathogens.