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

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.
Competing Interests: Declaration of interests D.M., E.C.A., P.H., K.-J.J.P., M.A., H.B., A.D., Y.B., B.C., J.V., S.R, J.A.G., M.S., R.Y., W.T., K.T., S.P., P.K., J.D., S.M.S., B.M.S, S.G.H., and P.C. are employees of Arcturus Therapeutics, Inc. E.E.O is an unpaid member of the Scientific Advisory Board of Arcturus Therapeutics, Inc.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)