Current advancements and potential strategies in the development of MERS-CoV vaccines

Abstract

Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.

Keywords: MERS-CoV; Middle East respiratory syndrome; adjuvants; administration routes; coronavirus; receptor-binding domain; spike protein; subunit vaccines; vaccines.

Figure 1.

Laboratory confirmed cases of human infection with MERS-coronavirus. The black columns indicate the total laboratory confirmed human cases infected with MERS-CoV, while the gray columns demonstrate the total deaths caused by MERS-CoV infection from September 2012 to the indicated date.

Figure 2.

Genomic and schematic diagram of MERS-coronavirus structure. (A) MERS-CoV genomic structure. Viral genes, including ORF 1a, ORF 1b, S, 3, 4a, 4b, 5, E, M, 8b and N (GenBank accession number: JX869059) and their respective lengths, are indicated by rectangular boxes in the scheme. (B) Schematic diagram of MERS-CoV structure. MERS-CoV contains four structural proteins. The S protein is a type I transmembrane glycoprotein displayed on the surface of viral membrane as an oligomer. The E protein is also a transmembrane protein that forms an ion channel on the viral surface. The N protein plays an important role in encapsidating the genomic RNA and interacting with the membrane M protein and other N molecules.

Figure 3.

Schematic diagrams of spike protein structures of representative coronaviruses. Schematic diagrams of the structures of S proteins of the previously identified coronaviruses NL63-CoV, MHV-CoV, SARS-CoV (A), and the newly emerged coronavirus MERS-CoV (B) are indicated. The S proteins contain S1 and S2 subunits, respectively, with RBDs located in the S1 region. RBMs are functional regions within RBDs for receptor recognition. Other functional domains, such as fusion peptide, HR1, HR2, transmembrane and cytoplasmic tail, contain variant lengths within different coronaviruses.

Figure 4.

Crystal structures of SARS-CoV and MERS-CoV RBD and neutralizing epitopes on SARS-CoV RBD. (A) Crystal structure of SARS-CoV RBD complexed with its receptor ACE2 (blue) (PDB ID: 2AJF) [31]. (B) Neutralizing epitope for mAb m396 Fab on SARS-CoV RBD (PDB ID: 2DD8) [41]. SARS-CoV RBD is in black with RBM region in yellow. (C) Neutralizing epitope for mAb F26G19 Fab on SARS-CoV RBD (PDB ID: 3BGF) [40]. (D) Neutralizing epitope for mAb 80R scFv on SARS-CoV RBD (PDB ID: 2GHW) [42]. (E) Crystal structure of MERS-CoV RBD. The RBM is in yellow. (PDB ID: 4KQZ) [36]. (F) Crystal structure of MERS-CoV RBD (black) complexed with its receptor human DPP4 (blue) (PDB ID: 4KR0) [37].