The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques

• DOI: 10.1371/journal.ppat.1008339
• Publication Date: 2020-03-12T17:52:03Z
• Authors: Gabriela M. Webb; Jhomary Molden; Kathleen Busman-S...; Shaheed Abdulhaqq; Helen L. Wu; Whitney C. Weber; Katherine B. Bateman; Jason S. Reed; Mina Northrup; Nicholas Maier; Shiho Tanaka; Lina Gao; Brianna Davey; Benjamin L. Carpe...; Michael K. Axthelm; Jeffrey J. Stanton; Jeremy Smedley; Justin M. Greene; Jeffrey T. Safrit; Jacob D. Estes; Pamela J. Skinner; Jonah B. Sacha
• Keywords: Interleukin 15

Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative there remains an urgent need develop approaches clear latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into field as potential "shock kill" therapeutic for cure. However, ability reactivate virus modulate anti-viral immunity in vivo under cover ART undefined. Here, we show ART-suppressed, simian-human immunodeficiency (SHIV)SF162P3-infected rhesus macaques, subcutaneous administration activates mobilizes both NK cells SHIV-specific CD8+ T from peripheral blood lymph node B cell follicles, sanctuary site normally excludes such effector cells. We observed minimal activation memory CD4+ no increase RNA content resident post administration. Accordingly, found difference number or magnitude plasma viremia timepoints between treated untreated animals during period, size DNA cell-associated reservoir treatment. These results substantiate immunotherapeutic candidate capable activating directing follicle full suppression, suggest must be paired bona fide latency reversing agent facilitate immune-mediated modulation