Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model

ABSTRACT

Genetic optimization of Nucleic Acid immunogens is important for potentially improving their immune potency. A COVID-19 DNA vaccine is in phase III clinical trial which is based on a promising highly developable technology platform. Here, we show optimization in mice generating a pGX-9501 DNA vaccine encoding full-length spike protein, which results in induction of potent humoral and cellular immune responses, including neutralizing antibodies, that block hACE2-RBD binding of live CoV2 virus in vitro. Optimization resulted in improved induction of cellular immunity by pGX-9501 as demonstrated by increased IFN-γ expression in both CD8+ and CD4 + T cells and this was associated with more robust antiviral CTL responses compared to unoptimized constructs. Vaccination with pGX-9501 induced subsequent protection against virus challenge in a rigorous hACE2 transgenic mouse model. Overall, pGX-9501 is a promising optimized COVID-19 DNA vaccine candidate inducing humoral and cellular immunity contributing to the vaccine’s protective effects.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• spike protein
• DNA vaccine
• protective response
• wild-type sequence
• optimizations

Acknowledgments

David Weiner was supported in part by the WW.Smith Trust and the Wistar Corona Virus Discovery Fund. We wish to thank Dr. David Hokey for his proofreading and editing.

Disclosure statement

D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and received fees for consulting, including serving on scientific review committees, SAB, and BOD functions. Remuneration received by D.B.W. includes direct payments, stock, or stock options, and in the interest of disclosure, D.B.W. discloses the following paid associations with commercial partners: Pfizer (Advisory Board), Geneos (Advisory, SRA), Advaccine (Advisory) Astrazeneca (Advisory, Speaker), Inovio (BOD, SRA, Stock ownership), Sanofi (Advisory Board), BBI (Advisory Board, SRA).

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2021.2016201

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81991492]; National Natural Science Foundation of China [82041039]; National Key R&D Program of Chinese Ministry of Science & Technology [2018YFC0840402].