An overview of current COVID-19 vaccine platforms

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that emerged in December 2019 in Wuhan city, China. An effective vaccine is urgently needed to protect humans and to mitigate the economic and societal impacts of the pandemic. Despite standard vaccine development usually requiring an extensive process and taking several years to complete all clinical phases, there are currently 184 vaccine candidates in pre-clinical testing and another 88 vaccine candidates in clinical phases based on different vaccine platforms as of April 13, 2021. Moreover, three vaccine candidates have recently been granted an Emergency Use Authorization by the United States Food and Drug Administration (for Pfizer/BioNtech, Moderna mRNA vaccines, and Johnson and Johnson viral vector vaccine) and by the UK government (for University of Oxford/AstraZeneca viral vector vaccine). Here we aim to briefly address the current advances in reverse genetics system of SARS-CoV-2 and the use of this in development of SARS-CoV-2 vaccines. Additionally, we cover the essential points concerning the different platforms of current SARS-CoV-2 vaccine candidates and the advantages and drawbacks of these platforms. We also assess recommendations for controlling the COVID-19 pandemic and future pandemics using the benefits of genetic engineering technology to design effective vaccines against emerging and re-emerging viral diseases with zoonotic and/or pandemic potential.

Keywords: Platforms; Reverse genetics system; SARS-CoV-2; Vaccines; mRNA.

Graphical abstract

Fig. 1

Genome Organization of SARS-CoV-2. The SARS-CoV-2 RNA genome is ~ 30 kb in length and is organized into at least 11 open reading frames (ORFs). The viral genome is capped at the 5′ end and polyadenylated at the 3′ ends. ORF1a and ORF1b, which occupy the two-thirds of the viral genome, encode the nonstructural proteins (nsp1 to nsp16), whereas the four structural proteins, which include the spike (S), envelope (E), membrane (M), and nucleocapsid (N), are encoded by the structural genes. In addition, accessory proteins are also encoded by the structural genes. Identified cis-acting regulatory elements are also shown at the 5′ end (SL1 to SL8), at the ORF1a/b frameshifting region (FSE), and at the 3′ untranslated region. SL: stem-loop; TRS: transcriptional regulatory sequence; FSE: frameshifting element; PK: pseudoknot; HVR: hypervariable region.

Fig. 2

Summary of SARS-CoV-2 Vaccine platforms. A) Live-attenuated vaccine platform in which SARS-CoV-2 is engineered by RG system to produce modified vaccine seed that is used for vaccine production in susceptible cells such as Vero E6 cells. B) Inactivated virus vaccine platform whereby SARS-CoV-2 prepared vaccine seed is propagated (scaled-up) in Vero E6 cells and is then chemically inactivated and finally formulated with a specific adjuvant. C) Protein subunit platform in which whole or part of spike protein, such as the receptor-binding domain, is expressed in mammalian or insect cells and/or yeast, purified, and finally mixed with a specific adjuvant. D) Viral vector platform (replication-deficient adenovirus) in which the adenovirus genome is modified by RG, the open reading frame (ORF) of the spike protein is cloned into adenovirus genome, and finally infectious recombinant virus is rescued in complementing cells. The final rescued virus is adenovirus expressing SARS-CoV-2 spike protein. E) Genetic vaccine (plasmid DNA vaccine) in which SARS-CoV-2 spike ORF is cloned into a plasmid DNA under a strong promoter such as that of human cytomegalovirus, and then, the plasmid is scaled-up in bacteria and finally purified. The final purified plasmid is inoculated into humans using an electroporation gun. F) Genetic vaccine (mRNA vaccine) in which SARS-CoV-2 spike mRNA is chemically synthesized and enclosed with lipid nanoparticles for efficient delivery into human cells. This figure was created with BioRender (https://bioRender.com/).

Fig. 3

Schematic design of recombinant NDV and MV constructs. A) The gene of interest (GOI) is designed according to the rule of six with consideration of sequences of gene end (GE), intergenic sequence (IS), and gene start (GS) of next gene and is cloned into P and M junction of NDV LaSota strain antigenomic cDNA that is under the T7 RNA polymerase promoter (T7p) and the T7 RNA polymerase terminator (T7t) sequence to obtain highest gene expression. B) Schematic design of the recombinant measles virus (MV) vector construct. The GOI is designed according to the rule of six with consideration of sequences as above and is cloned into the full-length viral antigenomic cDNA of the measles such as Schwarz vaccine and cloned at various positions to obtain either high or low protein expression dependent on the insertion site (arrows indication). MV genes: N (nucleoprotein), PVC (phosphoprotein and V/C proteins), M (matrix), F (fusion), H (hemagglutinin), L (polymerase), T7p (T7 RNA polymerase promoter), hh (hammerhead ribozyme), T7t (T7 RNA polymerase terminator), and (hepatitis delta virus ribozyme).