Sherazaan Ismail

This session focused on a variety of advances in immunology. These included insight into the increased risk of atherosclerosis in PLWH on ART, changes in the TCR repertoire shortly after HIV infection, improvements in HIV mRNA vaccine design, and mechanisms of post-treatment control that involve synergy between different immune subsets.

Dr. Tomas Salinas (Université de Montréal) described factors associated with atherosclerosis development in PLWH on ART, including higher fibrinogen levels, decreased frequencies of Th17 cells, lower Th17:Treg ratios, highly activated and diminished CCR9-expressing non-classical monocytes. Compromise of the gut mucosa in PLWH due to depletion of Th17 cells contributes to immunological alterations linked with atherosclerosis. Magalli Magnoumba Lenganga (Africa Health Research Institute) performed a longitudinal analysis of the TCR repertoire in the FRESH cohort. Significant skewing of the TCR repertoire occurred after HIV acquisition, and networking analysis identified clusters of TCRs specific for similar HIV epitopes. Dr. Paolo Lusso (LIR, NIAID) presented improvements in mRNA vaccine design with the addition of HIV protease (gag+pol) to lipid nanoparticles containing env and gag mRNA. This addition resulted in increased formation of mature VLPs. Immunization of mice with the env+gag+pol mRNA vaccine resulted in higher production of neutralizing antibodies (primarily CD4-binding site-directed). Dr Nuria Vidal presented a case study of a woman who has maintained virological control for 15 years after treatment interruption. Control was not associated with genetic factors but with 3-fold higher NKG2C+ memory-like NK cells and 6-fold higher levels of CD8+γδ+ T cells than referenced data from untreated progressors.

Subclinical atherosclerosis was only evaluated in PLWH and not the HIV-uninfected participants in the study to tease apart whether the same or different mechanisms underlie atherosclerosis in uninfected individuals. Magalli Magnoumba’s approach can be used to identify antigens for incorporation into CAR T cells as an HIV cure intervention. She noted that one participant had a large proportion of γδ CD8 T cells, indicating that there may be a link between her findings and Dr. Vidal’s. Further studies into the phenotype of these expanded TCRs and linking reservoir estimates in the FRESH cohort is a potential avenue of future work.