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Abstract

The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across the globe at an unprecedented rate since its first emergence in Wuhan City, China in December 2019. Scientific communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine development. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical trials, including their antigenic targets, delivery vehicles, and route of administration. Important features of previous gene-based vaccine developments against other infectious diseases are discussed in guiding the design and development of effective vaccines against COVID-19 and future derivatives.

Keywords: COVID-19; Coronavirus; DNA vaccines; Non-replicative viral vaccines; RNA vaccines; Replicative viral vaccines; SARS-CoV-2; Vaccines.

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Conflict of interest statement

Declaration of Interests None.

Figures

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Graphical abstract
Fig. 1
Fig. 1
Overview of current COVID-19 vaccine development efforts. For each vaccine platform, the number of corresponding vaccine candidates are identified in parentheses. While protein subunit vaccines are the single most common vaccine candidate, gene-based vaccine development efforts overall outnumber all other platforms. Vaccine candidate numbers are based on the WHO Draft landscape of COVID-19 Candidate Vaccines [6].
Fig. 2
Fig. 2
SARS-CoV-2 genome and schematic representation of the structural proteins. a) The open reading frames (ORFs) that encode for the replicase polyprotein (ORF1a and 1b), structural and accessory proteins are indicated in boxes. b) Schematic representation of the four major structural proteins Spike, Envelope, Membrane and Nucleocapsid produced to assemble progeny virions. c) The S1 and S2 subunits of the Spike protein are indicated in blue boxes. The Receptor Binding Domain (RBD) which directly binds to the angiotensin converting enzyme 2 (ACE2) receptor of the host cell is highlighted.
Fig. 3
Fig. 3
Protein identity comparison between SARS-CoV-2 strains from different countries and related betacoronavirus strains. The SARS-CoV-2 isolates demonstrate 100% identity across all regions, whereas the SARS-CoV and MERS-CoV strains show some variance. Amino acid sequences for all alignments were obtained from NCBI GenBank. Percent identities were obtained using BLASTp and are listed above or below their corresponding regions: spike (S), membrane (M), nucleocapsid (N), envelope (E), receptor binding domain (RBD), S1 and S2.
Fig. 4
Fig. 4
Timeline of clinical trials undertaken by GBV candidates. Vaccines are grouped based on platform: viral, DNA, then RNA. Based on early data, many vaccine candidates have begun subsequent phases before the end of earlier trials. Several vaccine candidates have concurrent clinical trials; for these, their earliest and most recent ongoing trials are depicted.
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References

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