Built-in RNA-mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

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

Research output: Contribution to journalArticlepeer-review

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 nonimmunogenic. 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 nonimmunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.

Original languageEnglish
Pages (from-to)1990-2007
Number of pages18
JournalBiotechnology and Bioengineering
Volume117
Issue number7
DOIs
Publication statusPublished - 2020 Jul 1

Bibliographical note

Funding Information:
This study was supported by grants from the Ministry of Food and Drug Safety of the Republic of Korea (grant numbers 16172MFDS199, 18172MFDS252, 16172MFDS268, and 16172MFDS363), National Research Foundation of Korea (NRF) funded by the Korea government (Ministry of Science and ICT) (NRF‐2018M3A9H4079358) and was partially supported by Graduate School of YONSEI University research scholarship grants in 2019.

Funding Information:
This study was supported by grants from the Ministry of Food and Drug Safety of the Republic of Korea (grant numbers 16172MFDS199, 18172MFDS252, 16172MFDS268, and 16172MFDS363), National Research Foundation of Korea (NRF) funded by the Korea government (Ministry of Science and ICT) (NRF-2018M3A9H4079358) and was partially supported by Graduate School of YONSEI University research scholarship grants in 2019.

Publisher Copyright:
© 2020 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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