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.
| Original language | English |
|---|---|
| Journal | mBio |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 11 Jul 2022 |
Bibliographical note
Funding Information:This study was supported by contract HHSN272201400006C from NIAID, NIH, USA. The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry.
Funding Information:
The Working group on the standardization of the ferret model for influenza risk assessment includes the following members: Elisabeth Blanchard and Taronna R. Maines (Centers for Disease Control and Prevention, USA), Ka-Tim Choy, Sin Fun Sia, and Wen Su (School of Public Health, The University of Hong Kong, China), Rebecca Frise and Jie Zhou (Imperial College, UK), Aeron C. Hurt (WHO Collaborating Centre for Reference and Research on Influenza, Doherty Institute, Australia), Chengjun Li (Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China), Theo Bestebroer, Dennis de Meulder, and Pascal Lexmond (Erasmus MC, The Netherlands), Shiho Chiba (University of Wisconsin, Madison, WI), Amar Bhagwat, Jennifer E. Jones, Karen A. Kormuth, and Valarie Le Sage (University of Pittsburgh, Pittsburgh, PA), C. Joaquin Caceres, Silvia Carnaccini, Lucas M. Ferreri, and Ginger Geiger (University of Georgia, USA), Jennifer L. DeBeauchamp, Meng Hu, Trushar Jeevan, and Lisa A. Kercher (St. Jude Children’s Research Hospital, USA), and Devanshi R. Patel, Kayla M. Septer, and Derek G. Sim (Pennsylvania State University, USA). This study was supported by contract HHSN272201400006C from NIAID, NIH, USA. The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry.
Publisher Copyright:
© 2022 Belser et al.
