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Built-in RNA-mediated Chaperone (Chaperna) for Antigen Folding Tailored to Immunized Hosts.

Identifieur interne : 000013 ( PubMed/Corpus ); précédent : 000012; suivant : 000014

Built-in RNA-mediated Chaperone (Chaperna) for Antigen Folding Tailored to Immunized Hosts.

Auteurs : Young-Seok Kim ; Jongkwan Lim ; Jemin Sung ; Yucheol Cheong ; Eun-Young Lee ; Jihoon Kim ; Hana Oh ; Yeon-Sook Kim ; Nam-Hyuk Cho ; Seongil Choi ; Sang-Moo Kang ; Jae-Hwan Nam ; Wonil Chae ; Baik L. Seong

Source :

RBID : pubmed:32297972

Abstract

High-quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA-dependent chaperone, in which the target antigen is genetically fused with an RNA-interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N-terminal tRNA-binding domain of lysyl-tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the "self" RID tag remained non-immunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS-CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc-mediated effector function was demonstrated, which could be harnessed for the design of next-generation "universal" influenza vaccines. The non-immunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics and designer vaccines. This article is protected by copyright. All rights reserved.

DOI: 10.1002/bit.27355
PubMed: 32297972

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pubmed:32297972

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