The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), crossed the species barrier and started infecting humans in Wuhan, China, in late 2019. The unprecedented global pandemic initiated by SARS-CoV-2 has prompted scientists to work on developing a preventive vaccine urgently.
The SARS-CoV-2 virus is predominantly transmitted via respiratory droplets. It causes a range of symptoms such as fever, cough, and shortness of breath in most people. In some people, the infection can lead to severe pneumonia, hospitalization, and mortality.
Several virus isolates have been taken from infected patients to characterize SARS-CoV-2 and develop vaccines or drugs to fight infection. One such isolate obtained from a patient who traveled to the US from China, SARS-CoV-2 USA-WA1/2020, is widely used in SARS-CoV-2 research.
Several animal models of SARS-CoV-2, including hamsters, transgenic mice with the human ACE2 receptor, cats, and ferrets, have also been developed for research purposes. Ferrets are an established model of influenza transmission and immunity, and the efficacy of the influenza vaccine in ferrets correlates with the efficacy of the vaccine in humans. Although several intramuscular SARS-CoV-2 vaccine candidates are in various phases of clinical trials, it is not clear if they will offer protection against SARS-CoV-2 infection.
Examining SARS-CoV-2 transmission modes and protection against re-infection in ferret models
Recently, a team of researchers from The Pennsylvania State University and the Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS) studied the transmission modes of SARS-CoV-2 and the protection against re-infection in ferret models in work published on the preprint server, bioRxiv*. The researchers used the reference strain SARS-CoV-2 USA-WA1/2020 and examined the modes of transmission and if immunity acquired through a prior infection or vaccination can protect ferrets against infection.
Direct contact and respiratory transmission of SARS-CoV-2 USA WA1/2020 in ferrets
They found that the ferrets were semi-permissive to infection by the SARS-CoV-2 USA-WA1/2020 isolate. On assessing transmission at multiple time points through the detection of vRNA, direct contact transmission was found in 3/3 and 3/4 contact animals in 2 respective studies, while the respiratory transmission was detected in only 1/4 contact animals.
In order to assess the durability of immunity, the experiment was repeated in the ferrets 28 or 56 days after primary infection. Following re-challenging with the viral isolate, no infectious virus was found in the nasal wash samples of the ferrets. Moreover, vRNA levels in the nasal wash were several folds lower than that detected during primary infection, and the vRNA also cleared rapidly.
Intramuscular vaccination with SARS-CoV-2 S protein RBD did not offer protection against infection in ferrets
The researchers then used a prime-boost strategy and vaccinated the ferrets with the S-protein receptor-binding domain formulated as an oil-in-water adjuvant to determine if intramuscular vaccination offered protection against infection. Upon viral challenge, none of the vaccinated animals had protection against infection, and no significant differences were found in the vRNA levels or infectious virus titers in the nasal wash of the ferrets.
These findings demonstrate that direct contact is the primary mode of transmission of the SARS-CoV-2 USA-WA1/2020 strain in ferrets and SARS-CoV-2 immunity is intact for at least 56 days. The study also indicates that only vaccine strategies mimicking natural infection or inducing site-specific immunity can offer protection of the upper respiratory tract against SARS-CoV-2.
Significance of the study
The SARS-CoV-2 USA-WA1/2020 is a CDC reference strain used by multiple research labs across the US. In this study, the researchers show that direct contact is the predominant transmission mode of this SARS-CoV-2 strain in ferrets. They further demonstrate that ferrets had protection against re-infection even when neutralizing antibody levels were are low or undetectable.
Lastly, they show that intramuscular vaccination of the ferrets failed to induce sufficient antibodies against SARS-CoV-2, and the ferrets remained susceptible to infection of the upper respiratory tract. In conclusion, these studies suggest that in order to protect the upper respiratory tract, we require vaccines that mimic natural SARS-CoV-2 infection.
The authors hope that although initial human vaccines can help reduce disease burden, in order to prevent SARS-CoV-2 infections fully, vaccines that can induce immunity in the upper respiratory tract - just like the natural infection - will need to be developed.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Transmission and protection against re-infection in the ferret model with the SARS-CoV-2 USA-WA1/2020 reference isolate, Devanshi R. Patel, Cassandra J. Field, Kayla M. Septer, Derek G. Sim, Matthew J. Jones, Talia A. Heinly, Elizabeth A. McGraw, Troy C Sutton, bioRxiv 2020.11.20.392381; doi: https://doi.org/10.1101/2020.11.20.392381, https://www.biorxiv.org/content/10.1101/2020.11.20.392381v1