Transmission and protection against reinfection in the ferret model with the SARS-CoV-2 USA-WA1/2020 reference isolate

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has initiated a global pandemic, and several vaccines have now received emergency use authorization. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semipermissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of viral RNA (vRNA) at multiple time points, direct contact transmission was efficient to 3/3 and 3/4 contact animals in 2 respective studies, while respiratory droplet transmission was poor to only 1/4 contact animals. To determine if previously infected ferrets were protected against reinfection, ferrets were rechallenged 28 or 56 days postinfection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets, ferrets were vaccinated using a primeboost strategy with the S protein receptor-binding domain formulated with an oil-inwater adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined, these studies demonstrate direct contact is the predominant mode of transmission of the USA-WA1/2020 isolate in ferrets and that immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity.