Breadth of viral inhibition is linked to T-cell polyfunctionality
PTE
POSITIVE
We next set out to see if similar associations exist between VIA breadth and T cell responses as measured by ICS. As a measure of T cell functionality upon peptide pool stimulation, T cells expressing multiple functional markers were measured and Combinatorial Polyfunctionality analysis of Antigen-Specific T-cell Subsets (COMPASS) analysis was performed. COMPASS allowed for the identification of antigen-specific changes across T cell subsets expressing IFN-γ, IL-2, TNF-α, CD40L, and IL-4 simultaneously or in various combinations, reducing this into a single score reflective of the extent of polyfunctional T cell responses induced (Stimulation with mosaic (Env, Gag, Pol) and PTE (Env) peptide pools revealed that CD4+ T cells had higher IFN-γ and/or IL-2 production as well as increased polyfunctionality scores to stimulation with Env peptide pools, compared to Gag and Pol pools, whereas CD8+ T cells responded better overall to Gag and Pol peptide pools and vaccine-insert matched Env pools (Fig. S3; Positive correlation between VIA responses and CD4 polyfunctionality (PFS) scores to PTE Env and between CD8 PFS to Mos Env and Gag scores. (VIA breadth scores demonstrated low to moderately strong Pearson correlations with IFN-y and/or IL-2 expressing T cells (Fig. S3), and stronger Pearson correlations with polyfunctionality scores (PFS). VIA breadth scores and polyfunctionality scores to each of the peptide pools tested for both CD4 and CD8+ T cells demonstrated significantly positive correlations for the Env3 PTE peptide pool and the RT Mos1 pool on CD4+ T cells (