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Polyvalent mRNA vaccination elicited potent immune response to monkeypox surface antigens

Zhenhao Fang, Paul A. Renauer, Kazushi Suzuki, Sidi Chen
doi: https://doi.org/10.1101/2022.11.29.518427
Zhenhao Fang
1Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
2System Biology Institute, Yale University, West Haven, CT, USA
3Center for Cancer Systems Biology, Yale University, West Haven, CT, USA
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Paul A. Renauer
1Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
2System Biology Institute, Yale University, West Haven, CT, USA
3Center for Cancer Systems Biology, Yale University, West Haven, CT, USA
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Kazushi Suzuki
1Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
2System Biology Institute, Yale University, West Haven, CT, USA
3Center for Cancer Systems Biology, Yale University, West Haven, CT, USA
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Sidi Chen
1Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
2System Biology Institute, Yale University, West Haven, CT, USA
3Center for Cancer Systems Biology, Yale University, West Haven, CT, USA
4Immunobiology Program, Yale University, New Haven, CT, USA
5Molecular Cell Biology, Genetics, and Development Program, Yale University, New Haven, CT, USA
6MD-PhD Program, Yale University, New Haven, CT, USA
7Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA
8Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA
9Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT, USA
10Wu-Tsai Institute, Yale University, New Haven, CT, USA
11Center for RNA Science and Medicine, Yale University, New Haven, CT, USA
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  • For correspondence: sidi.chen@yale.edu
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Abstract

The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 29, 2022.
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Polyvalent mRNA vaccination elicited potent immune response to monkeypox surface antigens
Zhenhao Fang, Paul A. Renauer, Kazushi Suzuki, Sidi Chen
bioRxiv 2022.11.29.518427; doi: https://doi.org/10.1101/2022.11.29.518427
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Polyvalent mRNA vaccination elicited potent immune response to monkeypox surface antigens
Zhenhao Fang, Paul A. Renauer, Kazushi Suzuki, Sidi Chen
bioRxiv 2022.11.29.518427; doi: https://doi.org/10.1101/2022.11.29.518427

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