Background
Much of the HIV reservoir resides in tissues such as the gut-associated lymphoid tissue (GALT). Broadly neutralizing antibodies (bNAbs) are under investigation for their potential to aid elimination of latently infected cells; however, little is known about their effect in key tissues such as the GALT. Here, we aim to study the effects of bNAbs on intestinal immune cells.
Methods
Study participants with suppressed HIV infection on antiretroviral treatment (ART) receiving a single infusion of two long-acting bNAbs (3BNC117-LS and 10-1074-LS) were prospectively enrolled and underwent colonoscopy at baseline and at 6-8 weeks post-infusion. Freshly processed ileal and colonic tissue biopsies were analyzed using single-cell RNA sequencing (scRNA-seq). The R-based package, Seurat, and the Enrichr platform were used for data analysis.
Results
Tissue samples were obtained from five study participants at baseline. Post-infusion tissue was available for two participants, yielding an aggregated dataset of 85,899 cells with 28,504 unique molecular identifiers (UMIs). Median (range) participant age was 55 (30-63) years old. Participants had been diagnosed with HIV for 17 (5-30) years with nadir and enrolment CD4+ T cell count of 249 (193-400) and 681 (440-1,113) cells/uL, respectively. Baseline CD4+ T cells in the ileum and colon were characterized by expression of pathways involved in regulatory T lymphocyte development (IL2, IL2RA, CTLA4, FOXP3) and tumor necrosis factor (TNF)/nuclear factor kappa B (NF-kB) signalling (LTA, LTB, TNFSF). Baseline CD8+ T cells were characterized by expression of pathways involved in chemokine receptor signalling (CCL4, CCR9) and lymphoid and non-lymphoid cell immunoregulatory interactions (CD247, ZAP70). Post-infusion CD4+ and CD8+ T cells showed significantly lower expression of pathways related to TNF/NF-kB and interferon signalling (NFKBIA, TNFAIP3, IFNG, STAT1).
Conclusions
In this pilot study, we identified transcriptional changes in GALT-resident immune cells of individuals with well-controlled HIV infection on ART following the infusion of 3BNC117-LS and 10-1074-LS bNAbs. These changes suggest that bNAb exposure may modulate TNF/NF-kB and IFN signalling in CD4+ and CD8+ T cells – pathways that have been linked to immune cell susceptibility to HIV infection, innate and adaptive immune response to HIV and reactivation of latent infection.
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