A DNA Vaccine Encoding the Full-Length Spike Protein of Beta Variant (B.1.351) Elicited Broader Cross-Reactive Immune Responses against Other SARS-CoV-2 Variants

Abstract

The SARS-CoV-2 pandemic remains an ongoing threat to global health with emerging variants, especially the Omicron variant and its sub-lineages. Although large-scale vaccination worldwide has delivered outstanding achievements for COVID-19 prevention, a declining effectiveness to a different extent in emerging SARS-CoV-2 variants was observed in the vaccinated population. Vaccines eliciting broader spectrum neutralizing antibodies and cellular immune responses are urgently needed and important. To achieve this goal, rational vaccine design, including antigen modeling, screening and combination, vaccine pipelines, and delivery, are keys to developing a next-generation COVID-19 vaccine. In this study, we designed several DNA constructs based on codon-optimized spike coding regions of several SARS-CoV-2 variants and analyzed their cross-reactive antibodies, including neutralizing antibodies, and cellular immune responses against several VOCs in C57BL/6 mice. The results revealed that different SARS-CoV-2 VOCs induced different cross-reactivity; pBeta, a DNA vaccine encoding the spike protein of the Beta variant, elicited broader cross-reactive neutralizing antibodies against other variants including the Omicron variants BA.1 and BA.4/5. This result demonstrates that the spike antigen from the Beta variant potentially serves as one of the antigens for multivalent vaccine design and development against variants of SARS-CoV-2.

Potent immunogenicity and broad-spectrum protection potential of microneedle array patch-based COVID-19 DNA vaccine candidates encoding dimeric RBD chimera of SARS-CoV and SARS-CoV-2 variants

“…As shown in Figure 1 (G), pAD1002 and pADV131 induced reasonably strong IgG responses in mice, whilst pAD1003 was essentially non-immunogenic. In an earlier study, we characterized a SARS-CoV-2 FL S protein-encoding construct, pWT, which required EP assistance to trigger decent humoral responses in vivo [ 32 ]. Like pAD1003, plasmid pWT was unable to elicit RBD-specific IgG production in mice when IM administered without EP ( Figure 1 (H)).…”

“…Complete antigen-encoding DNA sequences of the 3 plasmid constructs are given in the Supplemental File SF-1. Plasmid pWT, a pVAX1-based COVID-19 vaccine candidate encoding FL S protein of SARS-CoV-2, was as previously described [ 32 ]. A pVAX1-based expression plasmid encoding FL firefly luciferase (pVAX1-Luc) was similarly constructed.…”

A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies Against Multiple SARS-CoV-2 Variants Including the Currently Circulating Omicron BF.5, BF.7, BQ.1 and XBB

“…Several groups have explored the possibility to develop S protein-, or RBD-, encoding DNA vaccines against COVID-19, delivered by EP or needless injection (18–21). In consistence with our recent work showing that MAPs can effectively substitute EP and needless injection for DNA vaccine delivery in animal models of different genetic backgrounds (22), MAP-based pAD1016 also exhibited strong immunogenicity in generating strong adaptive immune responses in mice and rabbits.…”

“…DNA vaccines are considered an attractive alternative to conventional vaccines because they are relatively easy and inexpensive to produce, stable at room temperature, and able to stimulate robust cellular as well as humoral immunity (16,17). Several groups have explored the possibility to develop various DNA vaccines against COVID-19 with promising results (18)(19)(20). For example, COVID-eVax, an electroporated DNA vaccine candidate encoding the ancestral SARS-CoV-2 RBD, elicited protective responses in animal models (19).…”

A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB

“…DNA vaccines are considered an attractive alternative to conventional vaccines because they are relatively easy and inexpensive to produce, stable at room temperature, safe to use and able to stimulate robust cellular as well as humoral immunity in vivo [16,17]. Several groups have explored the possibility of developing various DNA vaccines against COVID-19 with promising results [18][19][20]. For example, COVID-eVax, an electroporated DNA vaccine candidate encoding the ancestral SARS-CoV-2 RBD, elicited protective responses in animal models [19].…”