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. 2023 Jul;95(7):e28948.
doi: 10.1002/jmv.28948.

Robust and protective immune responses induced by heterologous prime-boost vaccination with DNA-protein dimeric RBD vaccines for COVID-19

Yaling An  1 , Gan Zhao  2 , Huixin Duan  1 , Ning Zhang  3 , Minrun Duan  4 , Senyu Xu  1 , Xueyuan Liu  5 , Yuxuan Han  1 , Tianyi Zheng  6 , Xin Li  3 , Jiawang Hou  2 , Zhiyu Zhang  2 , Yuhai Bi  3   7 , Xin Zhao  3 , Kun Xu  8 , Lianpan Dai  3 , Bin Wang  2 , George F Gao  1   3   8
Affiliations

Robust and protective immune responses induced by heterologous prime-boost vaccination with DNA-protein dimeric RBD vaccines for COVID-19

Yaling An et al. J Med Virol. 2023 Jul.

Abstract

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 TH 1-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.

Keywords: COVID-19; DNA vaccine; SARS-CoV-2; ZF2001; heterologous prime-boost immunization; immune responses.

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