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Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2

Zhenhao Fang, Lei Peng, Qianqian Lin, Liqun Zhou, Luojia Yang, Yanzhi Feng, Ping Ren, Paul A. Renauer, Jonathan J. Park, Xiaoyu Zhou, Craig B. Wilen, Sidi Chen
doi: https://doi.org/10.1101/2022.03.22.485418
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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Lei Peng
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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Qianqian Lin
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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Liqun Zhou
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
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Luojia Yang
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
5Molecular Cell Biology, Genetics, and Development Program, Yale University, New Haven, CT, USA
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Yanzhi Feng
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
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Ping Ren
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
5Molecular Cell Biology, Genetics, and Development Program, Yale University, New Haven, CT, USA
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Jonathan J. Park
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
6MD-PhD Program, Yale University, New Haven, CT, USA
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Xiaoyu Zhou
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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Craig B. Wilen
7Department of Immunobiology, Yale University, New Haven, CT, USA
8Department of Laboratory Medicine, Yale University, New 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
9Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA
10Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA
11Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT, USA
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  • For correspondence: sidi.chen@yale.edu
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Abstract

The Omicron sub-lineage BA.2 of SARS-CoV-2 has recently become dominant across many areas in the world in the on-going waves of COVID-19. Compared to the ancestral/wild-type (WT) virus, Omicron lineage variants, both BA.1 and BA.2, contain high number of mutations, especially in the spike protein, causing significant immune escape that leads to substantial reduction of vaccine and antibody efficacy. Because of this antigenic drift, BA.2 exhibited differential resistance profile to monoclonal antibodies than BA.1. Thus, it is important to understand whether the immunity elicited by currently available vaccines are effective against the BA.2 subvariant. We directly tested the heterotypic vaccination responses against Omicron BA.2, using vaccinated serum from animals receiving WT- and variant-specific mRNA vaccine in lipid nanoparticle (LNP) formulations. Omicron BA.1 and BA.2 antigen showed similar reactivity to serum antibodies elicited by two doses of WT, B.1.351 and B.1.617 LNP-mRNAs. Neutralizing antibody titers of B.1.351 and B.1.617 LNP-mRNA were ~2-fold higher than that of WT LNP-mRNA. Both homologous boosting with WT LNP-mRNA and heterologous boosting with BA.1 LNP-mRNA substantially increased waning immunity of WT vaccinated mice against both BA.1 and BA.2 subvariants. The BA.1 LNP-mRNA booster was ~3-fold more efficient than WT LNP-mRNA at elevating neutralizing antibody titers of BA.2. Together, these data provided a direct preclinical evaluation of WT and variant-specific LNP-mRNAs in standard two-dose and as boosters against BA.1 and BA.2 subvariants.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Co-first authors.

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 March 23, 2022.
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Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Zhenhao Fang, Lei Peng, Qianqian Lin, Liqun Zhou, Luojia Yang, Yanzhi Feng, Ping Ren, Paul A. Renauer, Jonathan J. Park, Xiaoyu Zhou, Craig B. Wilen, Sidi Chen
bioRxiv 2022.03.22.485418; doi: https://doi.org/10.1101/2022.03.22.485418
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Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Zhenhao Fang, Lei Peng, Qianqian Lin, Liqun Zhou, Luojia Yang, Yanzhi Feng, Ping Ren, Paul A. Renauer, Jonathan J. Park, Xiaoyu Zhou, Craig B. Wilen, Sidi Chen
bioRxiv 2022.03.22.485418; doi: https://doi.org/10.1101/2022.03.22.485418

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