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

Mol Ther. 2021 Jun 2;29(6):1970-1983. doi: 10.1016/j.ymthe.2021.04.001. Epub 2021 Apr 5.

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.

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