H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets

J. de Jonge, Irina Isakova-Sivak, Harry van Dijken, Sanne Spijkers, Justin Mouthaan, Rineke Klaassen-de Jong, Tatiana Smolonogina, Paul Roholl, Larisa Rudenko

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Abstract

Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model.

Original languageEnglish
Pages (from-to)991-1002
JournalMolecular Therapy
Volume24
Issue number5
DOIs
Publication statusPublished - 2016

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Bronchopneumonia
Attenuated Vaccines
Ferrets
Influenza Vaccines
Virus Replication
Viral Pneumonia
Viruses
Influenza in Birds
Hemagglutination
Hemagglutinins
Neuraminidase
Orthomyxoviridae
Viral Load
China
Pneumonia
Vaccines
Public Health
Morbidity
Lung
Mortality

Cite this

de Jonge, J. ; Isakova-Sivak, Irina ; van Dijken, Harry ; Spijkers, Sanne ; Mouthaan, Justin ; Klaassen-de Jong, Rineke ; Smolonogina, Tatiana ; Roholl, Paul ; Rudenko, Larisa. / H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets. In: Molecular Therapy. 2016 ; Vol. 24, No. 5. pp. 991-1002.
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abstract = "Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model.",
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de Jonge, J, Isakova-Sivak, I, van Dijken, H, Spijkers, S, Mouthaan, J, Klaassen-de Jong, R, Smolonogina, T, Roholl, P & Rudenko, L 2016, 'H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets', Molecular Therapy, vol. 24, no. 5, pp. 991-1002. https://doi.org/10.1038/mt.2016.23

H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets. / de Jonge, J.; Isakova-Sivak, Irina; van Dijken, Harry; Spijkers, Sanne; Mouthaan, Justin; Klaassen-de Jong, Rineke; Smolonogina, Tatiana; Roholl, Paul; Rudenko, Larisa.

In: Molecular Therapy, Vol. 24, No. 5, 2016, p. 991-1002.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets

AU - de Jonge, J.

AU - Isakova-Sivak, Irina

AU - van Dijken, Harry

AU - Spijkers, Sanne

AU - Mouthaan, Justin

AU - Klaassen-de Jong, Rineke

AU - Smolonogina, Tatiana

AU - Roholl, Paul

AU - Rudenko, Larisa

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AB - Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model.

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DO - 10.1038/mt.2016.23

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JO - Molecular Therapy

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SN - 1525-0016

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