Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses.

Ning Wang,Lanying Du,Jian Shang,Shibo Jiang

doi:10.3389/fmicb.2020.00298

Ning Wang, Lanying Du + Show 2 more

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Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.

Highlights

Coronaviruses (CoVs) belong to the subfamily Othocoronavirinae, in the family Coronaviridae of the order Nidovirales
Among all CoVs identified so far, seven have the ability to infect humans, including human coronavirus 229E (HCoV-229E) and human coronavirus NL63 (HCoV-NL63), which belong to alpha-CoVs (Hamre and Procknow, 1966; Chiu et al, 2005), as well as human coronavirus OC43 (HCoV-OC43), human coronavirus HKU1 (HCoV-HKU1), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged coronavirus (2019-nCoV), which are known to be beta-CoVs (Drosten et al, 2003; Ksiazek et al, 2003; Vabret et al, 2003; Woo et al, 2005; Zaki et al, 2012; Du et al, 2016b; Zhang et al, 2020; Zhu et al, 2020) (Figure 1)
Several MERS-CoV subunit vaccines have been designed based on the identified critical neutralizing domain of receptorbinding domain (RBD) fragment, including those expressed in a stable Chinese hamster ovary (CHO) cell line (S377-588-fragment crystallizable (Fc)), fusing with a trimeric motif foldon (RBDFd), or containing single or multiple mutations in the RBD of representative human and camel strains from the 2012–2015 MERS outbreaks (Tai et al, 2016, 2017; Nyon et al, 2018)

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Introduction

Coronaviruses (CoVs) belong to the subfamily Othocoronavirinae, in the family Coronaviridae of the order Nidovirales. 2016a Wang et al, 2015 Adney et al, 2019 Jiaming et al, 2017 Yang et al, 2014a aaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha.

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