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 ^TM) 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 prolong 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 IFN-γ and IL-4 positive CD4 ⁺ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/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.

Graphical Abstract

Abstract

The LUNAR COV-19 SARS-CoV-2 vaccine is a self-replicating RNA based vaccine that increases antigen expression and also duration of expression. This increased antigen expression combined with the self-activation of the innate immune system produces a low single dose vaccine that yields protective immunity against SARS-CoV-2 virus infection.