Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Viruses
2.2. Plasmids
2.3. Minigenome Assays
2.4. Virus Rescue
2.5. Virus Growth Kinetics
2.6. Plaque Assays
2.7. Animal Experiments
2.8. Enzyme-Linked Immunosorbent Assays (ELISAs)
2.9. Hemagglutination Inhibition (HAI) Assays
2.10. Evaluation of T Cell Responses
3. Results
3.1. Mutations of the US AA MDV and Russian Len MDV Confer Different Levels of Temperature Sensitivity to the Polymerase of PR8
3.2. Recombinant PR8/Len is More Temperature Sensitive than PR8/AA
3.3. Attenuation of PR8/Len and PR8/AA in a Mouse Model of Influenza Infection
3.4. Immune Responses and Protection Efficacy of PR8/Len and PR8/AA in Mice against a Homologous Viral Challenge
3.5. Immune Responses and Protection Efficacy of PR8/Len and PR8/AA Against a Heterologous Viral Challenge
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Rodriguez, L.; Blanco-Lobo, P.; Reilly, E.C.; Maehigashi, T.; Nogales, A.; Smith, A.; Topham, D.J.; Dewhurst, S.; Kim, B.; Martínez-Sobrido, L. Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines. Viruses 2019, 11, 928. https://doi.org/10.3390/v11100928
Rodriguez L, Blanco-Lobo P, Reilly EC, Maehigashi T, Nogales A, Smith A, Topham DJ, Dewhurst S, Kim B, Martínez-Sobrido L. Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines. Viruses. 2019; 11(10):928. https://doi.org/10.3390/v11100928
Chicago/Turabian StyleRodriguez, Laura, Pilar Blanco-Lobo, Emma C. Reilly, Tatsuya Maehigashi, Aitor Nogales, Andrew Smith, David J. Topham, Stephen Dewhurst, Baek Kim, and Luis Martínez-Sobrido. 2019. "Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines" Viruses 11, no. 10: 928. https://doi.org/10.3390/v11100928