Recombinant OC43 SARS-CoV-2 spike replacement virus: An improved BSL-2 proxy virus for SARS-CoV-2 neutralization...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Seasonal human coronaviruses (CoVs) and SARS-CoV-2 pose significant public health challenges.
• Developing safe and effective SARS-CoV-2 vaccines and diagnostic tools remains a priority.

Purpose of the Study:

• To engineer a replication-competent, attenuated human coronavirus (OC43) expressing the SARS-CoV-2 spike protein (rOC43-CoV2 S).
• To evaluate rOC43-CoV2 S as a live attenuated vaccine candidate and a tool for measuring SARS-CoV-2 specific antibodies.

Main Methods:

• Recombinant OC43 virus was engineered to express the SARS-CoV-2 spike protein.
• The attenuated virus (rOC43-CoV2 S) was characterized in cell culture and animal models.
• Immunogenicity and protective efficacy were assessed in human ACE2 transgenic mice and rhesus macaques.

Main Results:

• rOC43-CoV2 S is highly attenuated and classified as a biosafety level 2 agent.
• Neutralization of rOC43-CoV2 S and SARS-CoV-2 showed high correlation with S-specific antibodies.
• Single-dose immunization with rOC43-CoV2 S protected mice from lethal SARS-CoV-2 challenge and induced robust antibody responses in macaques.

Conclusions:

• rOC43-CoV2 S is a valuable biosafety level 2 agent for measuring SARS-CoV-2 S-specific antibodies.
• rOC43-CoV2 S is a promising candidate for a live attenuated SARS-CoV-2 mucosal vaccine, preferentially replicating in the upper airway.