An overview of Middle East respiratory syndrome coronavirus vaccines in preclinical studies

ABSTRACT

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) causes high mortality in humans. No vaccines are approved for use in humans; therefore, a consistent effort to develop safe and effective MERS vaccines is needed.

Areas covered

This review describes the structure of MERS-CoV and the function of its proteins, summarizes MERS vaccine candidates under preclinical study (based on spike and non-spike structural proteins, inactivated virus, and live-attenuated virus), and highlights potential problems that could prevent these vaccines entering clinical trials. It provides guidance for the development of safe and effective MERS-CoV vaccines.

Expert opinion

Although many MERS-CoV vaccines have been developed, most remain at the preclinical stage. Some vaccines demonstrate immunogenicity and efficacy in animal models, while others have potential adverse effects or low efficacy against high-dose or divergent virus strains. Novel strategies are needed to design safe and effective MERS vaccines to induce broad-spectrum immune responses and improve protective efficacy against multiple strains of MERS-CoV and MERS-like coronaviruses with pandemic potential. More funds should be invested to move vaccine candidates into human clinical trials.

KEYWORDS:

• Coronavirus
• MERS-CoV
• spike protein
• structural proteins
• non-structural proteins
• vaccines
• preclinical studies

Article highlights

• MERS-CoV, an emerging human coronavirus (CoV), belongs to the same β-genus as SARS-CoV and SARS-CoV-2. But MERS-CoV is distinctive from SARS-CoV and SARS-CoV-2: it is a member in lineage C, whereas SARS-CoV and SARS-CoV-2 are associated with lineage B, of β-CoV genus. MERS-CoV causes severe infections in humans, with a global fatality rate of about 34.4%; thus, there is an urgent need to design and develop novel vaccines that protect against MERS-CoV infection.

• MERS-CoV is a zoonotic CoV originating from bats, utilizing dromedary camels as its most important intermediate host. Camel-to-human and human-to-human transmission of MERS-CoV has been identified, although transmission between humans is limited.

• The genome of MERS-CoV encodes four major structural proteins (spike (S), nucleocapsid (S), membrane (M), and envelope (E)), 16 nsps, and five accessory proteins. The structure and/or function of some of these proteins have been determined, thereby providing a basis for the design of effective MERS vaccines.

• MERS-CoV recognizes human dipeptidyl peptidase 4 (hDPP4) as its cellular receptor to bind to target cells via the receptor-binding domain (RBD) within the S protein, thereby mediating virus entry and membrane fusion through the S2 region of the S protein. In addition to MERS-CoV, several MERS-like CoVs may also utilize hDPP4 as the receptor for cell entry.

• Most currently developed MERS vaccines are under preclinical development; these vaccines are based on the MERS-CoV S protein, non-S structural proteins (such as N protein), inactivated virus, or live-attenuated virus.

• MERS-CoV S protein is an important target for the development of MERS vaccines; the majority of the currently designed MERS vaccines are based on this protein. These vaccines can be further classified as DNA, viral vector, protein (subunit), VLP, BLP, and nanoparticle vaccines, most of which have been evaluated for immunogenicity and/or efficacy in mice. Some have been tested in camels and/or NHPs.

• MERS vaccines of each type have both advantages and disadvantages. Novel strategies are needed to design safe and effective vaccines to eliminate potential harmful effects, and preserve and/or improve the immunogenicity and efficacy of current MERS vaccines.

• At present, no MERS vaccines have been approved for use in humans, and only a very limited number (including those based on DNA and viral vectors) have been tested for immunogenicity and/or safety in phase I clinical trials. Lacking of sufficient funds prevents the progression of vaccines from preclinical studies to clinical trials. Therefore, more funding from all sources is anticipated to speed up progress to testing in humans.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The study was supported by the National Institutes of Health (NIH) grants [R01AI137472, R01AI157975, and R01AI139092].