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 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.

Lipid nanoparticles for mRNA delivery

“…Other COVID-19 vaccines based on lipid nanoparticle–mRNA formulations are also under evaluation in different clinical phases (Table 1 ). In preclinical studies, some vaccine candidates showed protective effects by delivering self-amplifying RNA encoding the spike protein 40 , 186 , 187 (Box 2 ), a cocktail of mRNAs encoding three viral proteins 74 , modified mRNA encoding the receptor-binding domain 188 or spike mRNA with engineered untranslated regions 107 .

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SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

“…The company Vaxart has developed a vaccine that uses a nrVV adenovirus type-5 (Ad5), that encodes the complete S glycoprotein as it is expressed by the original SARS-CoV-2, preserving all the components of the S1 and S2 subunits (64). Similarly, the company Arcturus Therapeutics has used a complete S glycoprotein without modifications, however, they have opted for technologies of a self-replicating mRNA ready for translation (65). Other companies such as AstraZeneca and CanSino Biologics have developed nrVV such as AZD1222 and Ad5-nCOV.…”

mRNA vaccines for infectious diseases: principles, delivery and clinical translation

“…It encodes the full-length prefusion spike protein. In transgenic mice expressing human angiotensin-converting enzyme 2, doses of 2 µg and 10 µg produced strong T cell responses, high IgG titres and protected mice from SARS-CoV-2 infection 137 . Although the ARCT-021 dose is higher than the LNP-nCoVsaRNA dose, no booster is required, ensuring that recipients are fully vaccinated after a single injection.…”