A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody...

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV), identified in 2012, poses a significant public health threat with a high case fatality rate (>30%) and pandemic potential.
• Despite the risks, no safe and effective vaccine against MERS-CoV is currently available.

Purpose of the Study:

• To design, characterize, and evaluate a novel MERS-CoV nanoparticle vaccine candidate for preclinical efficacy.
• To assess the immunogenicity and protective capabilities of the MERS-CoV vaccine in various animal models.

Main Methods:

• Development of a stabilized MERS-CoV spike antigen displayed on a self-assembling ferritin nanoparticle.
• Evaluation of vaccine immunogenicity in BALB/c mice and non-human primates (NHPs), including antibody neutralization assays and cross-reactivity assessments.
• Assessment of vaccine efficacy through MERS-CoV lethal challenge in human DPP4 transgenic mice and an alpaca challenge model.

Main Results:

• The nanoparticle vaccine candidate elicited strong MERS-CoV neutralizing antibody titers in mice and NHPs, with cross-reactivity against different MERS-CoV clades and a related merbecovirus.
• Immunization provided dose-dependent protection against MERS-CoV lethal challenge in human DPP4 transgenic mice.
• Complete protection against MERS-CoV infection was observed in alpacas using the vaccine candidate.

Conclusions:

• The MERS-CoV nanoparticle vaccine is a promising candidate for clinical development.
• This vaccine could offer protection for at-risk populations and serve as a crucial tool in potential outbreak scenarios.