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.
Keywords: COVID-19; LUNAR-COV19; SARS-CoV-2; STARR; conventional mRNA; coronavirus; self-amplifying RNA; vaccine.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Alphavirus / genetics
- Alphavirus / immunology
- Angiotensin-Converting Enzyme 2 / genetics
- Angiotensin-Converting Enzyme 2 / immunology
- Animals
- Antibodies, Neutralizing / biosynthesis*
- Antibodies, Viral / biosynthesis*
- CD8-Positive T-Lymphocytes / drug effects
- CD8-Positive T-Lymphocytes / immunology
- CD8-Positive T-Lymphocytes / virology
- COVID-19 / immunology
- COVID-19 / pathology
- COVID-19 / prevention & control*
- COVID-19 / virology
- COVID-19 Vaccines / administration & dosage*
- COVID-19 Vaccines / biosynthesis
- COVID-19 Vaccines / genetics
- COVID-19 Vaccines / immunology
- Female
- Gene Expression
- Humans
- Immunity, Cellular / drug effects
- Immunity, Humoral / drug effects
- Interferon-gamma / genetics
- Interferon-gamma / immunology
- Interleukin-4 / genetics
- Interleukin-4 / immunology
- Mice
- Mice, Transgenic
- Replicon / immunology
- SARS-CoV-2 / drug effects*
- SARS-CoV-2 / immunology
- SARS-CoV-2 / pathogenicity
- Spike Glycoprotein, Coronavirus / chemistry
- Spike Glycoprotein, Coronavirus / genetics
- Spike Glycoprotein, Coronavirus / immunology*
- Th1 Cells / drug effects
- Th1 Cells / immunology
- Th1 Cells / virology
- Transgenes
- Treatment Outcome
- Vaccination / methods
- Vaccines, Synthetic / administration & dosage*
- Vaccines, Synthetic / biosynthesis
- Vaccines, Synthetic / genetics
- Vaccines, Synthetic / immunology
- mRNA Vaccines
Substances
- Antibodies, Neutralizing
- Antibodies, Viral
- COVID-19 Vaccines
- IL4 protein, human
- Spike Glycoprotein, Coronavirus
- Vaccines, Synthetic
- spike protein, SARS-CoV-2
- Interleukin-4
- Interferon-gamma
- ACE2 protein, human
- Angiotensin-Converting Enzyme 2