A non-transmissible live attenuated SARS-CoV-2 vaccine

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Live attenuated vaccines (LAVs) administered mucosally present the full viral antigen repertoire and induce robust mucosal immunity, potentially offering superior protection against emerging SARS-CoV-2 variants compared to intramuscular non-replicating vaccines.
• A significant concern with LAVs is the risk of unintentional transmission, which could limit their clinical application.

Purpose of the Study:

• To investigate if removing the furin cleavage site (FCS) from the spike protein of a SARS-CoV-2 LAV candidate can prevent vaccine virus transmission without compromising efficacy.
• To assess the safety of the modified LAV in immunosuppressed animals and its potential for recombination.

Main Methods:

• A SARS-CoV-2 LAV candidate was engineered by removing the FCS from its spike protein.
• The efficacy, safety, and transmission potential of the modified LAV were evaluated in hamster models.
• In vitro and in vivo recombination assays were performed using a SARS-CoV-2 field strain.

Main Results:

• The attenuated SARS-CoV-2 LAV with an intact FCS and the one lacking the FCS induced virtually identical levels of protection and immunity.
• Complete abolition of horizontal vaccine virus transmission was observed between cohoused hamsters with the FCS-deleted LAV.
• The modified vaccine demonstrated safety in immunosuppressed animals and showed no tendency for recombination with a SARS-CoV-2 field strain.

Conclusions:

• Removal of the FCS from a SARS-CoV-2 LAV is a viable strategy to enhance vaccine safety by preventing transmission.
• This modification allows for the development of effective LAVs with reduced risk, potentially improving control of the COVID-19 pandemic.
• The FCS-deleted SARS-CoV-2 LAV represents a promising candidate for further development due to its efficacy, safety, and lack of transmissibility.