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

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-...

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Detalles Bibliográficos
Autores principales: Lovelace, Sarah E., Helmold Hait, Sabrina, Yang, Eun Sung, Fox, Madison L., Liu, Cuiping, Choe, Misook, Chen, Xuejun, McCarthy, Elizabeth, Todd, John-Paul, Woodward, Ruth A., Koup, Richard A., Mascola, John R., Pegu, Amarendra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490026/
https://www.ncbi.nlm.nih.gov/pubmed/36157588
http://dx.doi.org/10.1016/j.isci.2022.105067
Descripción
Sumario: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.