The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Viruses and Cells
2.2. Cold Adaptation of SARS-CoV-2 WA1
2.3. Plaque Assay and Selection of the Temperature-Sensitive SARS-CoV-2 Clones
2.4. Multiple-Step Growth Kinetics of SARS-CoV-2 TS11
2.5. RNA Extraction and Reverse Transcription-PCR
2.6. Next Generation Sequencing (NGS) and Sanger Sequencing
2.7. Experimental Infection of Syrian Hamsters with SARS-CoV-2
2.8. Histopathological Evaluation and Immunohistochemistry (IHC) for the Detection of SARS-CoV-2 Antigen
2.9. Measurement of Infectious Viral Titers and Serum Viral Neutralizing (VN) Antibody Titers
2.10. Statistical Analysis
3. Results
3.1. Generation of a Cold-Adapted and Temperature-Sensitive SARS-CoV-2 TS11
3.2. Characterization of the SARS-CoV-2 TS11 Mutant
3.3. Genomic Analysis of the SARS-CoV-2 TS11
3.4. SARS-CoV-2 TS11 Mutant Did Not Cause Clinical Disease in Syrian Hamsters Even following Co-Infection with WA1 Strain
3.5. TS11 Was Attenuated in Syrian Hamsters and Induced Protection against Clinical Disease following Challenge with a Heterologous SARS-CoV-2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nucleotide Position | WA1 | TS-11 | Protein | ||
---|---|---|---|---|---|
Nucleotide | Amino Acid | Nucleotide | Amino Acid | ||
344 | CTC | L | TTC | F | nsp1 |
548 | ATT | I | CTT | L | |
2393 | GTC | V | ATC | I | |
4200 | ATG | M | AAG | K | nsp3 |
4455 | GCC | A | GTC | V | |
5007 | ACG | T | ATG | M | |
5097 | ATT | N | AGT | S | |
7086 | ACT | T | ATT | I | |
15,240 | AAC | N | AAT | N | nsp12 |
16,411 | GAT | D | AAT | N | nsp13 |
19,893 | GAT | D | GAG | E | nsp15 |
20,863 | CAT | H | TAT | Y | nsp16 |
22,120 | TTC | F | TTT | F | S |
22,296 | CAT | H | CGT | R | |
23,594–23,629 | TNSPRRARSVAS | 36-nt-Del | 12-aa-Del | ||
24,000 | AGC | S | ATC | I | |
24,554 | ACA | T | GCA | A | |
26,339 | GCC | A | GTC | V | E |
26,571 | CTT | L | TTT | F | M |
26,907 | CTG | L | TTG | L | |
27,524 | TCA | S | TTA | L | orf7a |
27,807–28,177 | 371-nt-Del | deletion of aa 18–43 of orf7b; deletion of orf8 | |||
28,866 | ACT | T | ATT | I | N |
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Xu, J.; Liu, M.; Niu, X.; Hanson, J.; Jung, K.; Ru, P.; Tu, H.; Jones, D.M.; Vlasova, A.N.; Saif, L.J.; et al. The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine. Viruses 2023, 15, 95. https://doi.org/10.3390/v15010095
Xu J, Liu M, Niu X, Hanson J, Jung K, Ru P, Tu H, Jones DM, Vlasova AN, Saif LJ, et al. The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine. Viruses. 2023; 15(1):95. https://doi.org/10.3390/v15010095
Chicago/Turabian StyleXu, Jiayu, Mingde Liu, Xiaoyu Niu, Juliette Hanson, Kwonil Jung, Peng Ru, Huolin Tu, Daniel M. Jones, Anastasia N. Vlasova, Linda J. Saif, and et al. 2023. "The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine" Viruses 15, no. 1: 95. https://doi.org/10.3390/v15010095
APA StyleXu, J., Liu, M., Niu, X., Hanson, J., Jung, K., Ru, P., Tu, H., Jones, D. M., Vlasova, A. N., Saif, L. J., & Wang, Q. (2023). The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine. Viruses, 15(1), 95. https://doi.org/10.3390/v15010095