Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge
Abstract
:1. Introduction
2. Materials and Methods
2.1. Immunization of Black-Footed Ferrets
2.2. Serology
2.3. In Vivo Passive Serum Transfer Studies
2.4. Histopathology of Mice from Serum Transfer Study
2.5. Challenge of Vaccinated and Unvaccinated BFF with SARS-CoV-2 Virus
2.6. Analyses
3. Results
3.1. Ferret Immunization
3.2. Serology
3.3. Passive Serum Transfer Studies in Mice
3.4. Viral Loads by Treatment and by ELISA Antibody Titers in Mice
3.5. Histologic Examination of Tissues from Mice
3.6. SARS-CoV-2 Challenge in Black-Footed Ferrets
3.7. Histopathology of Challenged Black-Footed Ferrets
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ELISA Titers | PRNT50 Titers | ||||||
---|---|---|---|---|---|---|---|
Ferret | Age (Years) | Treatment | Pre-Vac | Pre-Boost | 2–3 Wk Post-Boost | 12 Wk Post-Boost | 2–3 Wk Post-Boost |
8593 | 4 | Vaccine | NA | 640 | 2560 | 640 | Neg |
8847 | 4 | Vaccine | 160 | 160 | 10,240 | 2560 | Neg |
8995 * | 3 | Vaccine | 160 | 2560 | 10,240 | 2560 | <32 |
9135 | 2 | Vaccine | 160 | 2560 | 10,240 | 640 | <16 |
9189 | 2 | Vaccine | 160 | 10,240 | 10,240 | 2560 | 256 |
9219 | 2 | Vaccine | 160 | 10,240 | 10,240 | 10,240 | <64 |
9337 | 1 | Vaccine | 40 | 10,240 | 10,240 | 2560 | <64 |
9371 | 1 | Vaccine | 40 | 10,240 | 10,240 | 2560 | 256 |
9422 | 1 | Vaccine | 160 | 10,240 | 40,960 | 2560 | 256 |
9469 | 1 | Vaccine | 160 | 10,240 | 10,240 | 2560 | <64 |
9476 | 1 | Vaccine | 160 | 640 | 10,240 | 2560 | Neg |
9568 | 1 | Vaccine | 40 | 2560 | 10,240 | 2560 | <64 |
9571 | 1 | Vaccine | 40 | 10,240 | 40,960 | 160 | <64 |
9576 | 1 | Vaccine | 40 | 10,240 | 40,960 | 160 | 256 |
9598 * | 1 | Vaccine | 160 | 160 | 2560 | 40 | Neg |
8710 * | 4 | Placebo | 160 | 160 | 160 | 160 | Neg |
8721 | 4 | Placebo | 160 | 160 | 160 | 160 | Neg |
8970 | 3 | Placebo | 160 | 160 | 160 | 160 | Neg |
9247 | 2 | Placebo | 160 | 160 | 160 | 160 | Neg |
9311 | 2 | Placebo | 160 | 160 | 160 | 160 | Neg |
9388 | 1 | Placebo | 40 | 40 | 40 | 40 | Neg |
9425 | 1 | Placebo | 160 | 160 | 160 | 160 | Neg |
9519 | 1 | Placebo | 40 | 40 | 40 | 40 | Neg |
9592 | 1 | Placebo | 160 | 160 | 160 | 40 | Neg |
Ferret | Vaccinated | PFU/mL—Oropharyngeal Swab | PFU/mL—Nasal Flush Fluid | ||||||
---|---|---|---|---|---|---|---|---|---|
Day 1 | Day 3 | Day 5 | Day 7 | Day 1 | Day 3 | Day 5 | Day 7 | ||
8822 | No | <10 | <10 | NA | NA | 40 | 1600 | NA | NA |
8305 | Yes | <10 | 5400 | NA | NA | 630 | 29,000 | NA | NA |
8847 | Yes | <10 | <10 | <10 | <10 | <10 | <10 | <10 | <10 |
8226 | No | <10 | 20 | <10 | 120 | 1500 | 18,000 | 1200 | 270 |
9072 | No | <10 | 140 | 10 | 130 | 90 | 1900 | <10 | 60 |
8215 | No | <10 | 60 | <10 | 10 | 60 | 18,000 | 470 | 280 |
Ferret | Vaccinated | Sex | Age | PRNT90 Titer | PFU/Gram—Day 3 Post-Challenge | |||
---|---|---|---|---|---|---|---|---|
Day 3 | Day 14 | Turbinates | Cranial Lung | Caudal Lung | ||||
8822 | No | M | 5 | <10 | NA | 2.8 × 104 | <100 | <100 |
8305 | Yes | F | 7 | <10 | NA | 4.8 × 107 | <100 | 1.8 × 107 |
8847 | Yes | M | 5 | 320 | 10,240 | NA | NA | NA |
8226 | No | F | 7 | <10 | 40 | NA | NA | NA |
9072 | No | M | 4 | <10 | 10 | NA | NA | NA |
8215 | No | M | 7 | <10 | 40 | NA | NA | NA |
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Leon, A.E.; Garelle, D.; Hartwig, A.; Falendysz, E.A.; Ip, H.S.; Lankton, J.S.; Tretten, T.N.; Spraker, T.R.; Bowen, R.; Rocke, T.E. Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge. Viruses 2022, 14, 2188. https://doi.org/10.3390/v14102188
Leon AE, Garelle D, Hartwig A, Falendysz EA, Ip HS, Lankton JS, Tretten TN, Spraker TR, Bowen R, Rocke TE. Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge. Viruses. 2022; 14(10):2188. https://doi.org/10.3390/v14102188
Chicago/Turabian StyleLeon, Ariel E., Della Garelle, Airn Hartwig, Elizabeth A. Falendysz, Hon S. Ip, Julia S. Lankton, Tyler N. Tretten, Terry R. Spraker, Richard Bowen, and Tonie E. Rocke. 2022. "Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge" Viruses 14, no. 10: 2188. https://doi.org/10.3390/v14102188
APA StyleLeon, A. E., Garelle, D., Hartwig, A., Falendysz, E. A., Ip, H. S., Lankton, J. S., Tretten, T. N., Spraker, T. R., Bowen, R., & Rocke, T. E. (2022). Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge. Viruses, 14(10), 2188. https://doi.org/10.3390/v14102188