Nucleic Acid Vaccines against SARS-CoV-2

Abstract

The coronavirus disease 2019 (COVID-19) has spread worldwide and imposed a substantial burden on human health, the environment, and socioeconomic development, which has also accelerated the process of nucleic acid vaccine development and licensure. Nucleic acid vaccines are viral genetic sequence-based vaccines and third-generation vaccines after whole virus vaccines and recombinant subunit vaccines, including DNA vaccines and RNA vaccines. They have many unique advantages, but there are many aspects that require optimization. Therefore, the purpose of this review is to discuss the research and development processes of nucleic acid vaccines, summarize the advantages and shortcomings, and propose further optimization strategies by taking COVID-19 vaccines as an example. Hopefully, this work can make a modest contribution in promoting the construction of emergency nucleic acid vaccine platforms and in avoiding the reemergence of similar public health emergencies.

Keywords: COVID-19; advantages and shortcomings; development process; nucleic acid vaccines; optimization.

Figure 1

Illustration of the research and development process for nucleic acid vaccines. The procedure involves an early design stage, clinical trial stage, review and approval stage, and post-market surveillance. The early design stage generally consists of searching for immunogens, designing vaccine structures, and determining toxicological effects and immune effects in animal models. The clinical trials mainly include phases Ⅰ–Ⅲ, targeting primarily practical applications to provide definitive evidence for the safety and efficacy of vaccines.

Figure 2

Schematic diagram of COVID-19 synthetic DNA and RNA vaccine constructs. Schematic diagram of COVID-19 synthetic DNA vaccine constructs (left), where plasmids containing the IgE leader sequence and SARS-CoV-2 spike protein insert are shown. Schematic diagram of COVID-19 synthetic RNA vaccine constructs (right), showing the S1 (N-terminal furin cleavage fragment), S2 (C-terminal furin cleavage fragment), and RBD (receptor-binding domain). The positions of the P2 mutation (K986P and V987P) are indicated.