Monoclonal antibody isolation and characterization

我们已经分离并广泛表征了近30个恒河猴源单抗，其中一些介导广泛而有效的SIV中和活性。这组新鉴定的SIV单克隆抗体将能够在SIV NHP模型中使用全猿猴、恒河猴衍生的单克隆抗体来评估HIV-1预防和治疗干预措施，从而避免与人源抗体的快速单克隆抗体清除、Fc错配以及与SIV相比，SHIV有限的遗传多样性相关的问题。

We have isolated and extensively characterized nearly 30 rhesus-derived mAbs, several of which mediate broad and potent neutralizing activity against SIV. This panel of newly identified SIV bnAbs will enable evaluation of HIV-1 prophylactic and therapeutic interventions using fully simian, rhesus-derived bnAbs in the SIV NHP model, thereby circumventing issues related to rapid mAb clearance of human-derived antibodies, Fc mismatch and limited genetic diversity of SHIV compared to SIV. These SIV bnAbs have been used in structure-based studies to i) determine the co-crystal structure of SIVmac239 gp120 which revealed functional similarity between the SIV and HIV-1 glycan shields, and ii) obtain a cryo-EM structure of pre-fusion stabilized SIV trimer and an in-situ structure of SIVmac239 Env trimer on the surface of virions. Additionally, several SIV bnAbs are being produced by Quality Biological, Inc., the reagent contractor laboratory for the Vaccine Research Program (VRP), Preclinical Research and Development Branch (PRDB), Division of AIDS (DAIDS), to test whether they can be used for i) in vivo imaging of SIV infection in infected macaques (Paolo Lusso, M.D., Ph.D., Laboratory of Immunoregulation); ii) in a HIV-1 cure strategy combining latency reversal agents (LRA) and SIV bnAbs in a NHP model (Ann Chahroudi, MD, PhD, Emory University School of Medicine) iii) as bnAb therapy administered to (ART)-suppressed SIV-infected rhesus macaques (Louis Picker, Oregon National Primate Research Center) and iv) evaluation of antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent neutrophil phagocytosis (ADNP) of passive administered SIV mAbs and bnAbs (Galit Alter, PhD, Ragon Institute of MGH, MIT, and Harvard)