IL-15/IL-15RA CYTOKINE THERAPY ENHANCES CONTROL OF VIRAL REBOUND IN SIV-INFECTED MACAQUES

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B951
Abstract ID: 6283

Presenting Author:
Vijayakumar Velu , Assistant Professor at Emory Univ. Sch. of Med.

Abstract:

Immunotherapeutic cytokines such as IL-15 enhance follicular CD8 and IL-15 + IL-12 enhances follicular NK cells during chronic SIV infection. Here we tested the therapeutic effects of IL-15 and IL-12 administered alone or in combination during chronic SIV  in rhesus macaques (RMs).

Twenty-two RMs infected with SIVmac251 were initiated on antiretroviral therapy (ART) at 8 weeks post-SIV for 9 months. Three groups of RMs received cytokine therapy - IL-15/IL-15Ra (n=6), IL-12 (n=5), IL-15/IL-15Ra+IL-12 (n=6) - in 2 phases (5 doses once a week). The 1st phase was administered at 6 weeks post-SIV (2 weeks before ART) and the 2nd phase was during ART at 12 weeks pre-ATI. ART alone (n=5) group served as the control.

IL-15/IL-15Ra and IL-15/IL-15R+IL-12 therapies induced significant expansion of Ki-67+ (proliferative), CXCR5 (follicular homing) SIV-specific CD8 T and CD16+ NK cells in blood and LN. Importantly, IL-15/IL-15Ra therapy resulted in the expansion of CD107a+CD8 T cells pre-ATI (P=0.03). Further, the blood transcriptomic profile displayed induction of cytolytic molecules (granzyme-B, perforin), Jak/Stat signaling pathway. Post-ATI, the IL-15/IL-15Ra treated animals showed 3-log lower viremia compared to other groups (p=0.004) with 83% of RMs <500 copies/ml at 20 weeks. SIV-specific CXCR5+, CD28+  CD8 T , CD16+ NK in blood, LN were associated with enhanced viral control. These studies define IL-15/IL-15Ra as a potentially effective immune therapy for HIV cure strategy.