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A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice.
Mol Ther. 2021 06 02; 29(6):1970-1983.MT

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 prolongs 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 interferon (IFN)γ and interleukin-4 (IL-4)-positive CD4+ T helper (Th) lymphocytes as well as anti-spike glycoprotein immunoglobulin G (IgG)2a/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.

Authors+Show Affiliations

Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore; Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore; Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore; Department of Infectious Disease, Singapore General Hospital, Singapore, Singapore.Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore; Department of Infectious Disease, Singapore General Hospital, Singapore, Singapore.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA. Electronic address: sean@arcturusrx.com.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Arcturus Therapeutics, Inc., 10628 Science Center Drive, San Diego, CA 92121, USA.Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore; Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33823303

Citation

de Alwis, Ruklanthi, et al. "A Single Dose of Self-transcribing and Replicating RNA-based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity in Mice." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 29, no. 6, 2021, pp. 1970-1983.
de Alwis R, Gan ES, Chen S, et al. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol Ther. 2021;29(6):1970-1983.
de Alwis, R., Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Low, J. G. H., Kalimuddin, S., Matsuda, D., Allen, E. C., Hartman, P., Park, K. J., Alayyoubi, M., Bhaskaran, H., Dukanovic, A., Bao, Y., Clemente, B., Vega, J., ... Ooi, E. E. (2021). A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Molecular Therapy : the Journal of the American Society of Gene Therapy, 29(6), 1970-1983. https://doi.org/10.1016/j.ymthe.2021.04.001
de Alwis R, et al. A Single Dose of Self-transcribing and Replicating RNA-based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity in Mice. Mol Ther. 2021 06 2;29(6):1970-1983. PubMed PMID: 33823303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. AU - de Alwis,Ruklanthi, AU - Gan,Esther S, AU - Chen,Shiwei, AU - Leong,Yan Shan, AU - Tan,Hwee Cheng, AU - Zhang,Summer L, AU - Yau,Clement, AU - Low,Jenny G H, AU - Kalimuddin,Shirin, AU - Matsuda,Daiki, AU - Allen,Elizabeth C, AU - Hartman,Paula, AU - Park,Kyoung-Joo Jenny, AU - Alayyoubi,Maher, AU - Bhaskaran,Hari, AU - Dukanovic,Adrian, AU - Bao,Yanjie, AU - Clemente,Brenda, AU - Vega,Jerel, AU - Roberts,Scott, AU - Gonzalez,Jose A, AU - Sablad,Marciano, AU - Yelin,Rodrigo, AU - Taylor,Wendy, AU - Tachikawa,Kiyoshi, AU - Parker,Suezanne, AU - Karmali,Priya, AU - Davis,Jared, AU - Sullivan,Brian M, AU - Sullivan,Sean M, AU - Hughes,Steve G, AU - Chivukula,Pad, AU - Ooi,Eng Eong, Y1 - 2021/04/05/ PY - 2021/02/19/received PY - 2021/03/26/revised PY - 2021/03/30/accepted PY - 2021/4/7/pubmed PY - 2021/4/7/medline PY - 2021/4/6/entrez KW - COVID-19 KW - LUNAR-COV19 KW - SARS-CoV-2 KW - STARR KW - conventional mRNA KW - coronavirus KW - self-amplifying RNA KW - vaccine SP - 1970 EP - 1983 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol Ther VL - 29 IS - 6 N2 - 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 prolongs 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 interferon (IFN)γ and interleukin-4 (IL-4)-positive CD4+ T helper (Th) lymphocytes as well as anti-spike glycoprotein immunoglobulin G (IgG)2a/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. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/33823303/A_single_dose_of_self_transcribing_and_replicating_RNA_based_SARS_CoV_2_vaccine_produces_protective_adaptive_immunity_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(21)00188-X DB - PRIME DP - Unbound Medicine ER -