Evaluation of an antibody to a4ß7 in the control of SIVmac239-nef-stop infection

Author:

Di Mascio, M [ORCID]

Lifson,Jeffrey [ORCID]

Srinivasula,Sharat [ORCID]

Kim,Insook [ORCID]

DeGrange, P [ORCID]

Keele,Brandon [ORCID]

Belli, A J [ORCID]

Reimann, K A [ORCID]

Wang, Y

Proschan, M [ORCID]

Lane, H C [ORCID]

Fauci, A S [ORCID]
Author Address

AIDS Imaging Research Section, Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA. mdimascio@niaid.nih.gov., AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Battelle/Charles River-Integrated Research Facility, NIAID Frederick, Frederick, MD 21702, USA., MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA., Laboratory of Immunoregulation, Division of Intramural Research, NIAID, NIH, Bethesda, MD 20892, USA., Biostatistics Research Branch, Division of Clinical Research, NIAID, NIH, Bethesda, MD 20852, USA.,

Abstract:

Treatment of SIV-infected rhesus macaques with short-term antiretroviral therapy (ART) and partially overlapping infusions of antibody to integrin a4ß7 was reported to induce durable posttreatment viral suppression. In an attempt to replicate those observations, we treated macaques infected with the same virus and with the same ART and monoclonal antibody (mAb) regimens (anti-a4ß7 versus control mAb). Sequencing demonstrated that the virus used was actually SIVmac239-nef-stop, not wild-type SIVmac239. A positive correlation was found at 2 weeks after infection between the frequency of repair of attenuated Nef-STOP virus to pathogenic Nef-OPEN and plasma SIV RNA levels. Levels of plasma viremia before the first antibody infusion and preinfection levels of a4ß7hi CD4+ T cells, but not treatment with antibody to a4ß7 , correlated with levels of viral replication upon discontinuation of all treatments. Follow-up plasma viremia, peripheral blood CD4+ T cell counts, and lymph node and rectal tissue viral load were not significantly different between anti-a4ß7 and control mAb groups. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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