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A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

Ruklanthi de Alwis, Esther S Gan, Shiwei Chen, Yan Shan Leong, Hwee Cheng Tan, Summer L Zhang, Clement Yau, Daiki Matsuda, Elizabeth Allen, Paula Hartman, Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Belle Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne Parker, Priya Karmali, Jared Davis, Sean M. Sullivan, Steve G. Hughes, Pad Chivukula, Eng Eong Ooi
doi: https://doi.org/10.1101/2020.09.03.280446
Ruklanthi de Alwis
1Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Esther S Gan
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Shiwei Chen
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Yan Shan Leong
1Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore
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Hwee Cheng Tan
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Summer L Zhang
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Clement Yau
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Daiki Matsuda
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Elizabeth Allen
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Paula Hartman
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Jenny Park
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Maher Alayyoubi
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Hari Bhaskaran
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Adrian Dukanovic
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Belle Bao
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Brenda Clemente
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Jerel Vega
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Scott Roberts
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Jose A. Gonzalez
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Marciano Sablad
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Rodrigo Yelin
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Wendy Taylor
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Kiyoshi Tachikawa
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Suezanne Parker
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Priya Karmali
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Jared Davis
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Sean M. Sullivan
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Steve G. Hughes
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Pad Chivukula
3Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego CA 92121
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Eng Eong Ooi
1Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore
2Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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  • For correspondence: engeong.ooi@duke-nus.edu.sg
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ABSTRACT

A self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR®-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4+ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.

Competing Interest Statement

Daiki Matsuda, Elizabeth Allen, Paula Hartma3, Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Belle Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne Parker, Priya Karmali, Jared Davis, Sean M. Sullivan, Steve G. Hughes, Pad Chivukula are salaried employees of Arcturus Therapeutics, Inc. San Diego CA

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 September 03, 2020.
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A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Ruklanthi de Alwis, Esther S Gan, Shiwei Chen, Yan Shan Leong, Hwee Cheng Tan, Summer L Zhang, Clement Yau, Daiki Matsuda, Elizabeth Allen, Paula Hartman, Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Belle Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne Parker, Priya Karmali, Jared Davis, Sean M. Sullivan, Steve G. Hughes, Pad Chivukula, Eng Eong Ooi
bioRxiv 2020.09.03.280446; doi: https://doi.org/10.1101/2020.09.03.280446
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A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Ruklanthi de Alwis, Esther S Gan, Shiwei Chen, Yan Shan Leong, Hwee Cheng Tan, Summer L Zhang, Clement Yau, Daiki Matsuda, Elizabeth Allen, Paula Hartman, Jenny Park, Maher Alayyoubi, Hari Bhaskaran, Adrian Dukanovic, Belle Bao, Brenda Clemente, Jerel Vega, Scott Roberts, Jose A. Gonzalez, Marciano Sablad, Rodrigo Yelin, Wendy Taylor, Kiyoshi Tachikawa, Suezanne Parker, Priya Karmali, Jared Davis, Sean M. Sullivan, Steve G. Hughes, Pad Chivukula, Eng Eong Ooi
bioRxiv 2020.09.03.280446; doi: https://doi.org/10.1101/2020.09.03.280446

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