tetano
Editor, Senior Moderator
J Med Virol
. 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[SUP] 1 [/SUP], Gan Zhao[SUP] 2 [/SUP], Huixin Duan[SUP] 1 [/SUP], Ning Zhang[SUP] 3 [/SUP], Minrun Duan[SUP] 4 [/SUP], Senyu Xu[SUP] 1 [/SUP], Xueyuan Liu[SUP] 5 [/SUP], Yuxuan Han[SUP] 1 [/SUP], Tianyi Zheng[SUP] 6 [/SUP], Xin Li[SUP] 3 [/SUP], Jiawang Hou[SUP] 2 [/SUP], Zhiyu Zhang[SUP] 2 [/SUP], Yuhai Bi[SUP] 3 7 [/SUP], Xin Zhao[SUP] 3 [/SUP], Kun Xu[SUP] 8 [/SUP], Lianpan Dai[SUP] 3 [/SUP], Bin Wang[SUP] 2 [/SUP], George F Gao[SUP] 1 3 8 [/SUP]
Affiliations
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 T[SUB]H[/SUB] 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.
. 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[SUP] 1 [/SUP], Gan Zhao[SUP] 2 [/SUP], Huixin Duan[SUP] 1 [/SUP], Ning Zhang[SUP] 3 [/SUP], Minrun Duan[SUP] 4 [/SUP], Senyu Xu[SUP] 1 [/SUP], Xueyuan Liu[SUP] 5 [/SUP], Yuxuan Han[SUP] 1 [/SUP], Tianyi Zheng[SUP] 6 [/SUP], Xin Li[SUP] 3 [/SUP], Jiawang Hou[SUP] 2 [/SUP], Zhiyu Zhang[SUP] 2 [/SUP], Yuhai Bi[SUP] 3 7 [/SUP], Xin Zhao[SUP] 3 [/SUP], Kun Xu[SUP] 8 [/SUP], Lianpan Dai[SUP] 3 [/SUP], Bin Wang[SUP] 2 [/SUP], George F Gao[SUP] 1 3 8 [/SUP]
Affiliations
- PMID: 37436839
- DOI: 10.1002/jmv.28948
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 T[SUB]H[/SUB] 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.