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::

• adjuvants
• administration routes
• coronavirus
• MERS-CoV
• Middle East respiratory syndrome
• receptor-binding domain
• spike protein
• subunit vaccines
• vaccines

Acknowledgements

We thank Yang Yang at the Department of Pharmacology, University of Minnesota Medical School for the structural analysis of SARS-CoV and MERS-CoV RBDs.

Financial and competing interests disclosure

This study was supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (AI109094). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• First identified in humans in June 2012, Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), and is currently causing increased human infections with high mortality.

• Belonging to lineage C of β-CoV, phylogenetically related to bat-HKU4 and bat-HKU5, MERS-CoV is the first known lineage C β-CoV associated with human infections.

• Human dipeptidyl peptidase 4 is an identified receptor for MERS-CoV, and the receptor-binding domain (RBD) of MERS-CoV has been mapped by crystal structure to the residues covering 367–588 or 367–606, respectively.

• A truncated RBD fragment containing a 212-amino acid (residues 377–588) of MERS-CoV S protein induced strong RBD-specific antibodies, blocking MERS-CoV RBD binding to viral receptor dipeptidyl peptidase 4 and effectively neutralizing MERS-CoV infection, providing promise for further development as a MERS candidate vaccine.

• MERS-CoV S protein and RBD-based subunit vaccines that contain multiple neutralizing epitopes possess high efficacy to induce strong neutralizing antibody responses and protective immunity against MERS-CoV infection, representing a direction for future design of effective MERS vaccines.

• Subunit vaccines formulated with suitable adjuvants and administered with appropriate routes have a high potential to enhance the immunogenicity of MERS candidate vaccines.

Notes