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A Universal Bacteriophage T4 Nanoparticle Platform to Design Multiplex SARS-CoV-2 Vaccine Candidates by CRISPR Engineering

Jingen Zhu, Neeti Ananthaswamy, Swati Jain, Himanshu Batra, Wei-Chun Tang, Douglass A. Lewry, Michael L. Richards, Sunil A. David, Paul B. Kilgore, Jian Sha, Aleksandra Drelich, Chien-Te K. Tseng, Ashok K. Chopra, Venigalla B. Rao
doi: https://doi.org/10.1101/2021.01.19.427310
Jingen Zhu
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Neeti Ananthaswamy
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Swati Jain
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Himanshu Batra
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Wei-Chun Tang
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Douglass A. Lewry
2Virovax LLC, Lawrence, KS 66047, USA
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Michael L. Richards
2Virovax LLC, Lawrence, KS 66047, USA
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Sunil A. David
2Virovax LLC, Lawrence, KS 66047, USA
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Paul B. Kilgore
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
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Jian Sha
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
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Aleksandra Drelich
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
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Chien-Te K. Tseng
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
4Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA
5Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
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  • For correspondence: rao@cua.edu sktseng@utmb.edu achopra@utmb.edu
Ashok K. Chopra
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
4Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA
5Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
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  • For correspondence: rao@cua.edu sktseng@utmb.edu achopra@utmb.edu
Venigalla B. Rao
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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  • For correspondence: rao@cua.edu sktseng@utmb.edu achopra@utmb.edu
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Abstract

A “universal” vaccine design platform that can rapidly generate multiplex vaccine candidates is critically needed to control future pandemics. Here, using SARS-CoV-2 pandemic virus as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates were engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include: expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers is found to be the most potent vaccine candidate in mouse and rabbit models. Without any adjuvant, this vaccine stimulated robust immune responses, both TH1 and TH2 IgG subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new type of nanovaccine design framework might allow rapid deployment of effective phage-based vaccines against any emerging pathogen in the future.

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. All rights reserved. No reuse allowed without permission.
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Posted January 20, 2021.
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A Universal Bacteriophage T4 Nanoparticle Platform to Design Multiplex SARS-CoV-2 Vaccine Candidates by CRISPR Engineering
Jingen Zhu, Neeti Ananthaswamy, Swati Jain, Himanshu Batra, Wei-Chun Tang, Douglass A. Lewry, Michael L. Richards, Sunil A. David, Paul B. Kilgore, Jian Sha, Aleksandra Drelich, Chien-Te K. Tseng, Ashok K. Chopra, Venigalla B. Rao
bioRxiv 2021.01.19.427310; doi: https://doi.org/10.1101/2021.01.19.427310
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A Universal Bacteriophage T4 Nanoparticle Platform to Design Multiplex SARS-CoV-2 Vaccine Candidates by CRISPR Engineering
Jingen Zhu, Neeti Ananthaswamy, Swati Jain, Himanshu Batra, Wei-Chun Tang, Douglass A. Lewry, Michael L. Richards, Sunil A. David, Paul B. Kilgore, Jian Sha, Aleksandra Drelich, Chien-Te K. Tseng, Ashok K. Chopra, Venigalla B. Rao
bioRxiv 2021.01.19.427310; doi: https://doi.org/10.1101/2021.01.19.427310

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