Lack of therapeutic efficacy of an antibody to α4β7 in SIVmac251-infected rhesus macaques

Peter Abbink; Noe B Mercado; Joseph P Nkolola; Rebecca L Peterson; Hubert Tuyishime; Katherine McMahan; Edward T Moseley; Erica N Borducchi; Abishek Chandrashekar; Esther A Bondzie; Arshi Agarwal; Aaron J Belli; Keith A Reimann; Brandon F Keele; Romas Geleziunas; Mark G Lewis; Dan H Barouch

doi:10.1126/science.aaw8562

Lack of therapeutic efficacy of an antibody to α₄β₇ in SIVmac251-infected rhesus macaques

Science. 2019 Sep 6;365(6457):1029-1033. doi: 10.1126/science.aaw8562. Epub 2019 Sep 5.

Authors

Peter Abbink¹, Noe B Mercado¹, Joseph P Nkolola¹, Rebecca L Peterson¹, Hubert Tuyishime¹, Katherine McMahan¹, Edward T Moseley¹, Erica N Borducchi¹, Abishek Chandrashekar¹, Esther A Bondzie¹, Arshi Agarwal¹, Aaron J Belli², Keith A Reimann², Brandon F Keele³, Romas Geleziunas⁴, Mark G Lewis⁵, Dan H Barouch^{6

7}

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
² MassBiologics of the University of Massachusetts Medical School, Boston, MA 02126, USA.
³ AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
⁴ Gilead Sciences, Foster City, CA 94404, USA.
⁵ Bioqual, Rockville, MD 20852, USA.
⁶ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. [email protected].
⁷ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

Abstract

Sustained virologic control of human immunodeficiency virus type 1 (HIV-1) infection after discontinuation of antiretroviral therapy (ART) is a major goal of the HIV-1 cure field. A recent study reported that administration of an antibody against α₄β₇ induced durable virologic control after ART discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (SIV) containing a stop codon in nef We performed similar studies in 50 rhesus macaques infected with wild-type, pathogenic SIVmac251. In animals that initiated ART during either acute or chronic infection, anti-α₄β₇ antibody infusion had no detectable effect on the viral reservoir or viral rebound after ART discontinuation. These data demonstrate that anti-α₄β₇ antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Retroviral Agents / therapeutic use
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / therapeutic use*
Antibodies, Viral / administration & dosage
Antibodies, Viral / therapeutic use*
Codon, Terminator
DNA, Viral / blood
HIV Infections / therapy
Integrin alpha4 / immunology*
Integrin beta Chains / immunology*
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome / blood
Simian Acquired Immunodeficiency Syndrome / drug therapy
Simian Acquired Immunodeficiency Syndrome / therapy*
Simian Acquired Immunodeficiency Syndrome / virology*
Simian Immunodeficiency Virus / genetics*
Simian Immunodeficiency Virus / immunology*
Simian Immunodeficiency Virus / physiology
Viral Load
Viral Regulatory and Accessory Proteins / genetics
Viral Regulatory and Accessory Proteins / immunology

Substances

Anti-Retroviral Agents
Antibodies, Monoclonal
Antibodies, Viral
Codon, Terminator
DNA, Viral
Integrin beta Chains
NEF protein, SIV
Viral Regulatory and Accessory Proteins
integrin beta7
Integrin alpha4

Abstract

Publication types

MeSH terms

Substances

Grants and funding