Monoclonal antibody isolation and characterization

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

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)