Blocking α4β7 integrin delays viral rebound in SHIVSF162P3-infected macaques treated with anti-HIV broadly neutralizing antibodies.

Abstract

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4β7 with an anti-α4β7 monoclonal antibody (Rh-α4β7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4β7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4β7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4β7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4β7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.

• Authors: Ines Frank, Mariasole Cigoli, Muhammad S Arif, Marissa D Fahlberg, Stephanie Maldonado, Giulia Calenda, Amarendra Pegu, Eun Sung Yang, Reda Rawi, Gwo-Yu Chuang, Hui Geng, Cuiping Liu, Tongqing Zhou, Peter D Kwong, James Arthos, Claudia Cicala, Brooke F Grasperge, James L Blanchard, Agegnehu Gettie, Christine M Fennessey, Brandon F Keele, Monica Vaccari, Thomas J Hope, Anthony S Fauci, John R Mascola, Elena Martinelli
• Journal: Science translational medicine (Sci Transl Med) Vol. 13 Issue 607 (08 18 2021) ISSN: 1946-6242 [Electronic] United States
• PMID: 34408080 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Broadly Neutralizing Antibodies
• HIV Antibodies
• Integrins
• integrin alpha4beta7

Topics

• Animals
• Antibodies, Neutralizing
• Antibodies, Viral
• Broadly Neutralizing Antibodies
• HIV Antibodies
• HIV Infections (drug therapy)
• HIV-1
• Integrins
• Macaca mulatta
• Simian Acquired Immunodeficiency Syndrome (drug therapy)
• Simian Immunodeficiency Virus