Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection

Authors

Ming Yang, Arizona State University
Haiyan Sun, Arizona State UniversityFollow
Huafang Lai, Arizona State UniversityFollow
Biswas Neupane, University of Southern MississippiFollow
Fengwei Bai, University of Southern MississippiFollow
Herta Steinkellner, University of Natural Resources and Life Sciences
Qiang Chen, Arizona State UniversityFollow

Document Type

Article

Publication Date

3-29-2023

School

Biological, Environmental, and Earth Sciences

Abstract

Monoclonal antibodies (mAb) against the envelope (E) protein of Zika virus (ZIKV) have shown great potential as therapeutics against the Zika epidemics. However, their use as a therapy may predispose treated individuals to severe infection by the related dengue virus (DENV) via antibody-dependent enhancement of infection (ADE). Here, we generated a broadly neutralizing flavivirus mAb, ZV1, with an identical protein backbone but different Fc glycosylation profiles. The three glycovariants, produced in wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants and in Chinese hamster ovary cells (ZV1^WT, ZV1^ΔXF, and ZV1^CHO), respectively, showed equivalent neutralization potency against both ZIKV and DENV. By contrast, the three mAb glycoforms demonstrated drastically different ADE activity for DENV and ZIKV infection. While ZV1^CHO and ZV1^ΔXF showed ADE activity upon DENV and ZIKV infection, ZV1^WT totally forwent its ADE. Importantly, all three glycovariants exhibited antibody-dependent cellular cytotoxicity (ADCC) against virus-infected cells, with increased potency by the fucose-free ZV1^ΔXF glycoform. Moreover, the in vivo efficacy of the ADE-free ZV1^WT was demonstrated in a murine model. Collectively, we demonstrated the feasibility of modulating ADE by Fc glycosylation, thereby establishing a novel approach for improving the safety of flavivirus therapeutics. Our study also underscores the versatile use of plants for the rapid expression of complex human proteins to reveal novel insight into antibody function and viral pathogenesis.

Publication Title

Vaccines

Volume

11

Issue

4

First Page

755

Last Page

755

Recommended Citation

Yang, M., Sun, H., Lai, H., Neupane, B., Bai, F., Steinkellner, H., Chen, Q. (2023). Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection. Vaccines, 11(4), 755-755.
Available at: https://aquila.usm.edu/fac_pubs/21694