Search

The coronavirus disease 2019 (COVID‐19) pandemic posed great impacts on public health. To fight against the pandemic, robust immune responses induced by vaccination are indispensable. Previously, we developed a subunit vaccine adjuvanted by aluminum hydroxide, ZF2001, based on the dimeric tandem‐repeat RBD immunogen, which has been approved for clinical use. This dimeric RBD design was also explored as an mRNA vaccine. Both showed potent immunogenicity. In this study, a DNA vaccine candidate encoding RBD‐dimer was designed. The humoral and cellular immune responses induced by homologous and heterologous prime‐boost approaches with DNA‐RBD‐dimer and ZF2001 were assessed in mice. Protection efficacy was studied by the SARS‐CoV‐2 challenge. We found that the DNA‐RBD‐dimer vaccine was robustly immunogenic. Priming with DNA‐RBD‐dimer followed by ZF2001 boosting induced higher levels of neutralizing antibodies than homologous vaccination with either DNA‐RBD‐dimer or ZF2001, elicited polyfunctional cellular immunity with a TH1‐biased polarization, and efficiently protected mice against SARS‐CoV‐2 infection in the lung. This study demonstrated the robust and protective immune responses induced by the DNA‐RBD‐dimer candidate and provided a heterologous prime‐boost approach with DNA‐RBD‐dimer and ZF2001. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]