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

de Alwis, R. M.; Gan, E. S.; Chen, S.; Leong, Y. S.; Tan, H. C.; Zhang, S. L.; Yau, C.; Matsuda, D.; Allen, E.; Hartman, P.; Park, J.; Alayyoubi, M.; Bhaskaran, H.; Dukanovic, A.; Bao, B.; Clemente, B.; Vega, J.; Roberts, S.; Gonzalez, J. A.; Sablad, M.; Yelin, R.; Taylor, W.; Tachikawa, K.; Parker, S.; Karmali, P.; Davis, J.; Sullivan, S. M.; Hughes, S. G.; Chivukula, P.; Ooi, E. E.

doi:10.1101/2020.09.03.280446

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bioRxiv · 10.1101/2020.09.03.280446

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

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Abstract

A self-transcribing and replicating RNA (STARR) based vaccine (LUNAR(R)-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-{gamma} 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 g and 10 g 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.

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de Alwis, R. M., Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Matsuda, D., Allen, E., Hartman, P., Park, J., Alayyoubi, M., Bhaskaran, H., Dukanovic, A., Bao, B., Clemente, B., Vega, J., Roberts, S., Gonzalez, J. A., Sablad, M., Yelin, R., Taylor, W., Tachikawa, K., Parker, S., Karmali, P., Davis, J., Sullivan, S. M., Hughes, S. G., Chivukula, P., Ooi, E. E.. 2020-09-03. A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice. https://doi.org/10.1101/2020.09.03.280446

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