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A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice.


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.

SUBMITTER: de Alwis R 

PROVIDER: S-EPMC8019652 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice.

de Alwis Ruklanthi R   Gan Esther S ES   Chen Shiwei S   Leong Yan Shan YS   Tan Hwee Cheng HC   Zhang Summer L SL   Yau Clement C   Low Jenny G H JGH   Kalimuddin Shirin S   Matsuda Daiki D   Allen Elizabeth C EC   Hartman Paula P   Park Kyoung-Joo Jenny KJ   Alayyoubi Maher M   Bhaskaran Hari H   Dukanovic Adrian A   Bao Yanjie Y   Clemente Brenda B   Vega Jerel J   Roberts Scott S   Gonzalez Jose A JA   Sablad Marciano M   Yelin Rodrigo R   Taylor Wendy W   Tachikawa Kiyoshi K   Parker Suezanne S   Karmali Priya P   Davis Jared J   Sullivan Brian M BM   Sullivan Sean M SM   Hughes Steve G SG   Chivukula Pad P   Ooi Eng Eong EE  

Molecular therapy : the journal of the American Society of Gene Therapy 20210405 6


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 cel  ...[more]

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