tetano
Editor, Senior Moderator
mBio
. 2022 Jul 11;e0117422.
doi: 10.1128/mbio.01174-22. Online ahead of print.
Robustness of the Ferret Model for Influenza Risk Assessment Studies: a Cross-Laboratory Exercise
Jessica A Belser[SUP] #[/SUP][SUP] 1 [/SUP], Eric H Y Lau[SUP] #[/SUP][SUP] 2 [/SUP], Wendy Barclay[SUP] 3 [/SUP], Ian G Barr[SUP] 4 [/SUP], Hualan Chen[SUP] 5 [/SUP], Ron A M Fouchier[SUP] 6 [/SUP], Masato Hatta[SUP] 7 [/SUP], Sander Herfst[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP], Seema S Lakdawala[SUP] 8 [/SUP], Leo Yi Yang Lee[SUP] 4 [/SUP], Gabriele Neumann[SUP] 7 [/SUP], Malik Peiris[SUP] 2 [/SUP], Daniel R Perez[SUP] 9 [/SUP], Charles Russell[SUP] 10 [/SUP], Kanta Subbarao[SUP] 4 11 [/SUP], Troy C Sutton[SUP] 12 [/SUP], Richard J Webby[SUP] 10 [/SUP], Huanliang Yang[SUP] 5 [/SUP], Hui-Ling Yen[SUP] 2 [/SUP], Working group on the standardization of the ferret model for influenza risk assessment
Affiliations
Abstract
Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment. IMPORTANCE Following detection of a novel virus, rapid characterization efforts (both in vitro and in vivo) are undertaken at numerous laboratories worldwide to evaluate the relative risk posed to human health. Aggregation of these data are critical, but the use of nonstandardized protocols can make interpretation of divergent results a challenge. For evaluation of virus transmissibility, a multifactorial trait which can only be evaluated in vivo, identifying intrinsic levels of variability between groups can improve the utility of these data, as well as ensure that experiments are performed with sufficient replication to ensure high confidence in compiled results. Using the ferret transmission model and two influenza A viruses, we conducted a multicenter standardization exercise to improve the interpretation of transmission data generated during risk assessment activities; this exercise serves as a model for future efforts employing both in vitro and in vivo models against possible pandemic pathogens.
Keywords: assay standardization; ferret model; influenza; pandemic risk assessment; transmissibility.
. 2022 Jul 11;e0117422.
doi: 10.1128/mbio.01174-22. Online ahead of print.
Robustness of the Ferret Model for Influenza Risk Assessment Studies: a Cross-Laboratory Exercise
Jessica A Belser[SUP] #[/SUP][SUP] 1 [/SUP], Eric H Y Lau[SUP] #[/SUP][SUP] 2 [/SUP], Wendy Barclay[SUP] 3 [/SUP], Ian G Barr[SUP] 4 [/SUP], Hualan Chen[SUP] 5 [/SUP], Ron A M Fouchier[SUP] 6 [/SUP], Masato Hatta[SUP] 7 [/SUP], Sander Herfst[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP], Seema S Lakdawala[SUP] 8 [/SUP], Leo Yi Yang Lee[SUP] 4 [/SUP], Gabriele Neumann[SUP] 7 [/SUP], Malik Peiris[SUP] 2 [/SUP], Daniel R Perez[SUP] 9 [/SUP], Charles Russell[SUP] 10 [/SUP], Kanta Subbarao[SUP] 4 11 [/SUP], Troy C Sutton[SUP] 12 [/SUP], Richard J Webby[SUP] 10 [/SUP], Huanliang Yang[SUP] 5 [/SUP], Hui-Ling Yen[SUP] 2 [/SUP], Working group on the standardization of the ferret model for influenza risk assessment
Affiliations
- PMID: 35862762
- DOI: 10.1128/mbio.01174-22
Abstract
Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment. IMPORTANCE Following detection of a novel virus, rapid characterization efforts (both in vitro and in vivo) are undertaken at numerous laboratories worldwide to evaluate the relative risk posed to human health. Aggregation of these data are critical, but the use of nonstandardized protocols can make interpretation of divergent results a challenge. For evaluation of virus transmissibility, a multifactorial trait which can only be evaluated in vivo, identifying intrinsic levels of variability between groups can improve the utility of these data, as well as ensure that experiments are performed with sufficient replication to ensure high confidence in compiled results. Using the ferret transmission model and two influenza A viruses, we conducted a multicenter standardization exercise to improve the interpretation of transmission data generated during risk assessment activities; this exercise serves as a model for future efforts employing both in vitro and in vivo models against possible pandemic pathogens.
Keywords: assay standardization; ferret model; influenza; pandemic risk assessment; transmissibility.