Anti-viral efficacy of a next-generation CD4-binding site bNAb in SHIV-infected animals in the absence of anti-drug antibody responses

Sarah E Lovelace; Sabrina Helmold Hait; Eun Sung Yang; Madison L Fox; Cuiping Liu; Misook Choe; Xuejun Chen; Elizabeth McCarthy; John-Paul Todd; Ruth A Woodward; Richard A Koup; John R Mascola; Amarendra Pegu

doi:10.1016/j.isci.2022.105067

Anti-viral efficacy of a next-generation CD4-binding site bNAb in SHIV-infected animals in the absence of anti-drug antibody responses

iScience. 2022 Sep 5;25(10):105067. doi: 10.1016/j.isci.2022.105067. eCollection 2022 Oct 21.

Affiliation

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Abstract

Broadly neutralizing antibodies (bNAbs) against HIV-1 are promising immunotherapeutic agents for treatment of HIV-1 infection. bNAbs can be administered to SHIV-infected rhesus macaques to assess their anti-viral efficacy; however, their delivery into macaques often leads to rapid formation of anti-drug antibody (ADA) responses limiting such assessment. Here, we depleted B cells in five SHIV-infected rhesus macaques by pretreatment with a depleting anti-CD20 antibody prior to bNAb infusions to reduce ADA. Peripheral B cells were depleted following anti-CD20 infusions and remained depleted for at least 9 weeks after the 1^st anti-CD20 infusion. Plasma viremia dropped by more than 100-fold in viremic animals after the initial bNAb treatment. No significant humoral ADA responses were detected for as long as B cells remained depleted. Our results indicate that transient B cell depletion successfully inhibited emergence of ADA and improved the assessment of anti-viral efficacy of a bNAb in a SHIV-infected rhesus macaque model.

Keywords: Drugs; Immunology; Virology.