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

Fan, F.; Zhang, X.; Zhang, Z.; Ding, Y.; Wang, L.; Xu, X.; Pan, Y.; Gong, F.-Y.; Jiang, L.; Kang, L.; Kou, Z.; Zhao, G.; Wang, B.; Gao, X.-M.

doi:10.1101/2022.12.01.518127

bioRxiv · 10.1101/2022.12.01.518127

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

Fan, F.·Zhang, X.·Zhang, Z.·Ding, Y.·Wang, L.·Xu, X.·Pan, Y.·Gong, F.-Y.·Jiang, L.·Kang, L.·Kou, Z.·Zhao, G.·Wang, B.·Gao, X.-M.

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Abstract

Breakthrough infections by SARS-CoV-2 variants pose a global challenge to pandemic control, and the development of more effective vaccines of broadspectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding heterodimeric receptor-binding domain (RBD) chimera of SARS-CoV and SARS-CoV-2 Omicron BA.1 (RBDSARS/BA1), SARS-CoV and SARS-CoV-2 Beta (RBDSARS/Beta), or Omicron BA.1 and Beta (RBDBA1/Beta) in secreted form. When i.m. injected in mice, RBDSARS/BA1 and RBDSARS/Beta encoding plasmids (pAD1002 and pAD131, respectively) were by far more immunogenic than RBDBA1/Beta plasmid (pAD1003). Dissolvable microneedle array patches (MAP) laden with these DNA plasmids were fabricated. All 3 resulting MAP-based vaccine candidates, namely MAP-1002, MAP1003 and MAP-131, were comparable to i.m. inoculated plasmids with electroporation assistance in eliciting strong and durable IgG responses in BALB/c and C57BL/6 mice as well as rabbits, while MAP-1002 was comparatively the most immunogenic. More importantly, MAP-1002 significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-{gamma}+ T cells. Moreover, MAP-1002 antisera effectively neutralized pseudoviruses displaying spike proteins of SARS-CoV, prototype SARS-CoV-2 or Beta, Delta, Omicron BA1, BA2 and BA4/5 variants. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.

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Fan, F., Zhang, X., Zhang, Z., Ding, Y., Wang, L., Xu, X., Pan, Y., Gong, F.-Y., Jiang, L., Kang, L., Kou, Z., Zhao, G., Wang, B., Gao, X.-M.. 2022-12-02. 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. https://doi.org/10.1101/2022.12.01.518127

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