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™) 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.

COVID-19: Coronavirus Vaccine Development Updates

“…Mice vaccinated with a single dose of LUNAR-COV19 induced stronger T cell responses and significantly higher levels of S protein specific IgG lasting for 50 days after vaccination, as well as robust neutralizing antibodies. Similarly, Th1 biased immune responses were shown in this study, and LUNAR-COV19 also protected mice from SARS-CoV-2 lethal challenge and even measurable infection (124).…”

Nanomaterial Delivery Systems for mRNA Vaccines

“…The latter has three branches, resembling the Moderna Lipid H, but with a degradable thioester linked to the headgroup. A feature of self-amplifying mRNA was observed where luciferase reporter expression was maintained at a fairly constant level beyond one week of IM administration, while conventional mRNA expression fell quickly [ 58 ]. The vaccination alone surprisingly produced weight loss and increased clinical scores in C57BL/6 mice.…”

Self-assembled mRNA vaccines

“… In mice, 60 days after the administration of a single dose (2 μg or 10 μg) of the vaccine elicited robust CD8 + cell and CD4 + T H 1 cell response. [ 307 ] CVnCoV Prefusion-stabilized spike protein of SARS-CoV-2 LNP IM CureVac IIa In the phase I clinical trials, two doses were given in 4 weeks interval by IM injection. The vaccine was found to be safe with dose-dependent mild to moderate side effects.…”

“…ARCT-021 (LUNAR-COV19) is being developed by Arcturus Therapeutics and Duke-NUS Medical Center [ 307 ]. LUNAR-COV19 is a single dose, LNP-based vaccine that utilizes the proprietary self-transcribing and replicating RNA (STARR™) platform.…”