Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques

PloS One
Yvonne J RosenbergXiaoming Jiang

Abstract

Recombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by the introduction of defined mutations in the crystallizable fragment (Fc) domains eg YTE (M252Y/S254T/T256E) and LS (M428L/N434S), as a consequence of increased half-lives and prolonged duration of protection. However, the functional properties of any biologic may be compromised by unanticipated immunogenicity in humans, rendering them ineffective. Several potent broadly neutralizing HIV monoclonal antibodies (bnAbs) have been identified that protect against SHIV challenge in macaque models and reduce HIV viremia in HIV-infected individuals. In the present study, the pharmacokinetics and immunogenicity of one or more 5mg/kg subcutaneous (SC) injections in naïve macaques of the HIV bnAb PGT121 and its PGT121-YTE mutant, both produced in plants, have been compared towards prolonging efficacy. Induction of anti-drug/anti-idiotypic antibodies (ADA, anti-id) has been monitored using both binding ELISAs and more functional inhibition of virus neutralization (ID50) assays. Timing of...Continue Reading

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Citations

Dec 11, 2019·Antibodies·Mark L ChiuGary L Gilliland
Jun 15, 2021·Frontiers in Public Health·David A SpencerAnn J Hessell
Dec 7, 2021·Frontiers in Immunology·Wen Shi LeeStephen J Kent

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Methods Mentioned

BETA
ELISA
blood drawing
ELISAs
RNA assay

Software Mentioned

BIOQUAL
R package
PK Solutions
Excel

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