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Title: Pathogenicity testing of influenza candidate vaccine viruses in the ferret model

Abstract

The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenzamore » A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone in a mammalian model. - Highlights: • Confirmation of candidate vaccine viruses (CVVs) attenuation of virulence was demonstrated. • All influenza CVVs showed reductions in morbidity compared to wild-type (wt) viruses. • When compared with the wt viruses, all CVVs exhibited reductions in virus shedding in ferrets.« less

Authors:
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Publication Date:
OSTI Identifier:
22722973
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 511; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATTENUATION; DISEASE INCIDENCE; INFLUENZA VIRUSES; TESTING; VACCINES; VIRULENCE

Citation Formats

Belser, Jessica A., Johnson, Adam, Pulit-Penaloza, Joanna A., Pappas, Claudia, Pearce, Melissa B., Tzeng, Wen-Pin, Hossain, M. Jaber, Ridenour, Callie, Wang, Li, Chen, Li-Mei, Wentworth, David E., Katz, Jacqueline M., Maines, Taronna R., and Tumpey, Terrence M., E-mail: TTumpey@cdc.gov. Pathogenicity testing of influenza candidate vaccine viruses in the ferret model. United States: N. p., 2017. Web. doi:10.1016/J.VIROL.2017.08.024.
Belser, Jessica A., Johnson, Adam, Pulit-Penaloza, Joanna A., Pappas, Claudia, Pearce, Melissa B., Tzeng, Wen-Pin, Hossain, M. Jaber, Ridenour, Callie, Wang, Li, Chen, Li-Mei, Wentworth, David E., Katz, Jacqueline M., Maines, Taronna R., & Tumpey, Terrence M., E-mail: TTumpey@cdc.gov. Pathogenicity testing of influenza candidate vaccine viruses in the ferret model. United States. https://doi.org/10.1016/J.VIROL.2017.08.024
Belser, Jessica A., Johnson, Adam, Pulit-Penaloza, Joanna A., Pappas, Claudia, Pearce, Melissa B., Tzeng, Wen-Pin, Hossain, M. Jaber, Ridenour, Callie, Wang, Li, Chen, Li-Mei, Wentworth, David E., Katz, Jacqueline M., Maines, Taronna R., and Tumpey, Terrence M., E-mail: TTumpey@cdc.gov. 2017. "Pathogenicity testing of influenza candidate vaccine viruses in the ferret model". United States. https://doi.org/10.1016/J.VIROL.2017.08.024.
@article{osti_22722973,
title = {Pathogenicity testing of influenza candidate vaccine viruses in the ferret model},
author = {Belser, Jessica A. and Johnson, Adam and Pulit-Penaloza, Joanna A. and Pappas, Claudia and Pearce, Melissa B. and Tzeng, Wen-Pin and Hossain, M. Jaber and Ridenour, Callie and Wang, Li and Chen, Li-Mei and Wentworth, David E. and Katz, Jacqueline M. and Maines, Taronna R. and Tumpey, Terrence M., E-mail: TTumpey@cdc.gov},
abstractNote = {The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenza A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone in a mammalian model. - Highlights: • Confirmation of candidate vaccine viruses (CVVs) attenuation of virulence was demonstrated. • All influenza CVVs showed reductions in morbidity compared to wild-type (wt) viruses. • When compared with the wt viruses, all CVVs exhibited reductions in virus shedding in ferrets.},
doi = {10.1016/J.VIROL.2017.08.024},
url = {https://www.osti.gov/biblio/22722973}, journal = {Virology},
issn = {0042-6822},
number = ,
volume = 511,
place = {United States},
year = {Wed Nov 15 00:00:00 EST 2017},
month = {Wed Nov 15 00:00:00 EST 2017}
}