RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.01.518127
DO 10.1101/2022.12.01.518127
A1 Fan, Feng
A1 Zhang, Xin
A1 Zhang, Zhiyu
A1 Ding, Yuan
A1 Wang, Limei
A1 Xu, Xin
A1 Pan, Yaying
A1 Gong, Fang-Yuan
A1 Jiang, Lin
A1 Kang, Lingyu
A1 Kou, Zhihua
A1 Zhao, Gan
A1 Wang, Bin
A1 Gao, Xiao-Ming
YR 2022
UL http://biorxiv.org/content/early/2022/12/02/2022.12.01.518127.abstract
AB 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-γ+ 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.Competing Interest StatementFYG and YYP declare no competing interests. FF, GZ, XZ, YD, XX, ZK, ZZ, LW and XMG are Advaccine employees. LJ and KJ are Qinglan employees. GZ and BW are shareholders of Advaccine, LJ is a shareholder of Qinglan. GZ, FF, XMG and LJ are listed as inventors of pending patents for DNA- RBD-dimer design and/or MAP fabrication by Advaccine or Qinglan.