The Preclinical Evaluation of Self-Replicating RNA Oral Vaccine to Simultaneously Neutralize Both SARS-CoV-2 Delta and Alpha Variants

The aim of this study was to design an oral vaccine based on self-replicating RNA lipid nanoparticle (saRNA LNP) to neutralize SARS-CoV-2 Delta (B.1.617 lineage) and Alpha (B.1.1.7 lineage) variants. Before immunization of mice with saRNA LNP, we saw the high expression of S-protein at both mRNA and protein levels after transfection of HEK293T/17 with saRNA LNP. After immunization of BALB/c mice with saRNA LNP at 0.1-10 μg, a high quantity of SARS-CoV-2 specific IgG, IgG1, IgG2a, and IgA was seen with a dose-dependent and Th1/Th2 skewing response in serum of vaccinated mice. We also found that the secreted antibodies could neutralize SARS-CoV-2 Delta (B.1.617 lineage) and Alpha (B.1.1.7 lineage) variants. Splenocytes from vaccinated mice re-stimulated with SARS-CoV-2 peptides had high IFN-γ, IL-6, and TNF- α secretion. Although the preclinical study confirmed the efficacy of saRNA LNP against SARS-CoV-2, its efficacy and safety must be evaluated in clinical trials.