Coronavirus vaccine development: from SARS and MERS to COVID-19

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.

Keywords: Coronaviruses; SARS-CoV-2; Vaccine; Vaccine development.

Fig. 1

The genome and virion structure of coronaviruses (CoVs). a The genome structure of SARS-CoV, MERS-CoV, and SARS-CoV-2 [–14]. The 5′-terminus of the CoV genome contains two overlapping open reading frames (ORFs): ORF 1a and ORF 1b, spanning two-thirds of the genome length. ORF 1a and ORF 1ab can be translated into two polyproteins (pp), pp1a and pp1ab, which are further cleaved into 16 non-structural proteins (Nsps). The 3′-terminus of the CoV genome encodes four major structural proteins in the order of spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Genus-specific accessory proteins are also encoded at the 3′-terminus of the CoV genome. b The virion structure of SARS-CoV-2 [16]. The spike (S), envelope (E), membrane (M) proteins form the envelope of the CoV, and the nucleocapsid (N) proteins form the capsid to pack the genomic RNA. The spike protein binds to angiotensin converting enzyme 2 (ACE2) on the cell membrane, which allows the virus to enter the cell. (Created with BioRender.com.)

Fig. 2

The life cycle of SARS-CoV-2 [9, 10, 15]. Upon binding to the membrane receptor ACE2, SARS-CoV-2 virion enters the host cell and releases its plus-strand RNA genome. The plus-strand RNA translates pp1a and pp1ab, which are further cleaved into multiple non-structural proteins (Nsps) including an RNA-dependent RNA polymerase (Nsp12). The RNA-dependent RNA polymerase transcribes a negative-strand genomic RNA, and then uses this negative-strand genomic RNA as template to generate more plus-strand genomic RNA (genomic replication) and many different subgenomic RNAs (subgenomic transcription). The subgenomic RNAs are further translated into major structural proteins (N, S, M, E), which will assemble with plus-strand genomic RNA to form a mature virion in lumen of the ER. Finally, the whole virus leaves the cell through exocytosis. (Reprinted from “Coronavirus Replication Cycle”, by BioRender.com (2020). Retrieved from https://app.biorender.com/biorender-templates)