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

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Concep-tionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmis-sion of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV isa promising strategy to increase vac-cine safety and prevent vaccine transmission without compro-mising vaccine efficacy.

Automated summary

Live attenuated vaccines administered via the mucosal route may offer better control of the COVID-19 pandemic by presenting the entire antigenic repertoire of the virus and inducing strong mucosal immunity. Removal of the furin cleavage site from the spike protein of a SARS-CoV-2 LAV candidate can prevent vaccine transmission without compromising vaccine efficacy, as shown by the abolished horizontal transmission between cohoused hamsters and the safety of the vaccine in immunosuppressed animals.