Mentored Scientist Award

HIV affects nearly 40 million people worldwide, yet no cure exists. Significant efforts are being aimed at identifying therapeutic interventions that lead to durable control of HIV after ART interruption, termed post-intervention control (PIC). One intervention is broadly neutralizing antibody (bNAb) administration. bNAbs are well-known for their ability to neutralize HIV, but studies in HIV/SHIV suggest they may do more. In non-human primates, bNAb administration shortly after SHIV infection results in high rates of long-term SHIV control, likely mediated by CD8 T cells. In people with HIV, bNAb administration has been associated with reduced viral reservoir size, enhanced autologous antibody production, and increased T cell responses. The ability of bNAbs to potentiate an endogenous immune response is termed the “vaccinal effect”. This has been studied in the contexts of cancer and non- HIV viral infections but little is known about its role in HIV. We recently completed a combination immunotherapy trial of HIV PIC involving bNAb administration along with other therapeutic interventions and saw higher rates of PIC than any prior immune-based interventional study in HIV. The purpose of this grant is to investigate the role of the vaccinal effect in PIC of HIV in our study and more broadly. In Specific Aim 1, I will use existing and proposed longitudinal immunologic and virologic data collected from study participants during the period of bNAb-mediated viral suppression to look for evidence of immune activation. In Specific Aim 2, I will develop an in vitro model to study mechanisms underlying the vaccinal effect in the context of HIV. This project will significantly advance our understanding of HIV PIC and help inform future immune-based treatment strategies. It will also impart the skills I need to participate in studies of HIV and viral infections more broadly, and form the basis of future independent research grants.