A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice
| Autor: | Scott C. Roberts, Hwee Cheng Tan, Sean M. Sullivan, Suezanne Parker, Daiki Matsuda, Kiyoshi Tachikawa, Rodrigo Yelin, Jerel Vega, Clement Yau, Shirin Kalimuddin, Kyoung-Joo Jenny Park, Wendy Taylor, Jenny G. Low, Ruklanthi de Alwis, Eng Eong Ooi, Hari Bhaskaran, Summer L. Zhang, Maher Alayyoubi, Yan Shan Leong, Priya Karmali, Shiwei Chen, Jared Davis, Brian M. Sullivan, Brenda Clemente, Jose A. Gonzalez, Marciano Sablad, Esther S. Gan, Elizabeth C. Allen, Paula Hartman, Steve G. Hughes, Bao Yanjie, Adrian Dukanovic, Pad Chivukula |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
0303 health sciences biology viruses biochemical phenomena metabolism and nutrition Acquired immune system Virology Immunoglobulin G Vaccination 03 medical and health sciences 0302 clinical medicine Immune system Immunity 030220 oncology & carcinogenesis Drug Discovery Genetics biology.protein Molecular Medicine Replicon Neutralizing antibody Molecular Biology CD8 030304 developmental biology |
| Zdroj: | Molecular Therapy. 29:1970-1983 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2021.04.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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