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.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, coronavirus, self-amplifying RNA, LUNAR-COV19, STARR, conventional mRNA, 【초록키워드】 Vaccine, immune response, vaccination, Lymphocytes, Mortality, translation, SARS-COV-2 infection, spike glycoprotein, Infection, interferon, cytokine, CD4, CD8, RNA, replicon, human ACE2, lymphocyte, Immunoglobulin G, interleukin, Viral, Immunoglobulin, mice, SARS-CoV-2 spike glycoprotein, glycoprotein, expression, Antibody titers, Cell-mediated immunity, Anti-spike, IgG1, Neutralizing antibody titer, IL-4, dose, Interleukin-4, T helper, alphavirus, neutralizing antibody titers, complex, robust antibody responses, transgenic mice, wild-type SARS-CoV-2, ENCODE, full-length spike glycoprotein, Prevent, intracellular cytokine staining, produced, supported, amplify, T lymphocyte response, the SARS-CoV-2, 【제목키워드】 adaptive, Immunity, single dose, Protective, RNA-based SARS-CoV-2 vaccine,