Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice.

Abstract

The protective efficacies of current licensed vaccines againstCOVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern(VOCs) which carried multiple mutations in the Spike (S) protein. Considering thatthese vaccines were developed based on the S protein of the original SARS-CoV-2Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highlyconserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strainand the Omicron VOC. Literature mining and bioinformatics were used toidentify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S andmembrane (M) proteins. Nucleotide sequences encoding these peptides representinghighly conserved B and T cell epitopes were cloned into a pVAX1 vector to form thepVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine wasintranasally or intramuscularly administered to BALB/c mice and evaluations ofhumoral and cellular immune responses were performed. The intramuscularadministration of pVAX1/S2-6EHGFP was associated with a significantly higherpercentage of CD8+ T cells expressing IFN-γ when compared with the empty vectorand PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFPresulted in robust IgG antibody responses. Sera from mice intramuscularly immunizedwith pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable ofSARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This studydemonstrated that the DNA vaccine construct encoding highly conserved immunogenicB and T cell epitopes was capable of eliciting potent humoral and cellular immuneresponses in mice.