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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
Preprint
in En
| PREPRINT-BIORXIV
| ID: ppbiorxiv-518127
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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Collection:
09-preprints
Database:
PREPRINT-BIORXIV
Language:
En
Year:
2022
Document type:
Preprint