Angela Wahl

This session focused on the role of natural killer cells (NKs) and cytotoxic T lymphocytes (CTLs) in the control of SIV/HIV infection and how they can be harnessed and modulated to develop effective prophylactic and therapeutic vaccines, immunotherapies, and cure strategies.

Keith Reeves presented data from HVTN 087 and HVTN 094 demonstrating that HIV vaccines can elicit adaptive and memory NK responses. Peptide-specific adaptive NK responses were mediated by NKG2C. Sarah Rowland-Jones showed that CD8+ T cell-mediated viral control during HIV-2 infection is associated with gag responses. Gag-specific CD8+ T cells were polyfunctional, had high functional avidity, and maintained at high levels in absence of viremia. Lydie Trautmann showed that HIV-specific CD8+ T cells of RV254 participants treated during acute infection had limited PD-1 expression, preserved proliferation capacity, and superior killing capacity but their numbers were lower compared to chronic infection-treated individuals. Scott Kitchen showed that stem cell-based CAR therapy resulted in multiple lineages of CAR cells in non-human primates that were present in tissues and persisted for over 2 years. Compared to controls, animals receiving stem cell-based CARs had reduced viral rebound following ATI and lower SIV-RNA levels in tissue.

Future vaccine and cure strategies could exploit NK cells by tuning ADCC-mediating NK and inducing adaptive and memory NK responses by modulating the NKG2A/C-MHC-E axis. ART initiation during acute HIV infection combined with approaches to augment the frequency of HIV-specific CD8 T cells could boost CD8 T cell-mediated control HIV infection. In the studies presented, stem cell-based CAR therapy was administered prior to SIV infection, administration of stem cell-based CARs to ART-suppressed animals may more accurately predict the therapeutic efficacy of this approach as pre-conditioning regimens could impact efficacy.