Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Three highly pathogenic human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) have emerged, necessitating vaccines effective against Merbecovirus and Sarbecovirus subgenera.
• Current SARS-CoV-2 vaccines offer limited protection against other sarbecoviruses and merbecoviruses.

Purpose of the Study:

• To develop and evaluate a broadly protective vaccine against Merbecovirus and Sarbecovirus subgenera.
• To assess the efficacy of a trivalent nanoparticle vaccine in preclinical models.

Main Methods:

• Mice were vaccinated with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing receptor-binding domains (RBDs) from SARS-CoV-2, RsSHC014, and MERS-CoV.
• Neutralizing antibody responses and protection against live virus challenge in lethal mouse models were assessed.

Main Results:

• The trivalent RBD scNP vaccine elicited neutralizing antibodies against a range of coronaviruses, including WIV-1-CoV, SARS-CoV, SARS-CoV-2 variants, and MERS-CoV.
• Trivalent vaccine-protected mice against both Merbecovirus and Sarbecovirus challenge, unlike the monovalent SARS-CoV-2 vaccine which only protected against Sarbecovirus.

Conclusions:

• A single trivalent RBD scNP vaccine demonstrates proof of concept for broad protection against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
• This approach offers a potential strategy for developing pan-sarbecovirus and pan-merbecovirus vaccines.