H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets

Molecular Therapy : the Journal of the American Society of Gene Therapy
Jørgen de JongeL G Rudenko

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 lun...Continue Reading

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Citations

May 24, 2017·Expert Review of Vaccines·Irina Isakova-Sivak, Larisa Rudenko
Dec 21, 2016·Nature Communications·Martin M CorcoranGunilla B Karlsson Hedestam
Feb 12, 2019·Archives of Virology·Ainur NurpeisovaBerik Khairullin
Jun 4, 2020·Viruses·Irina KiselevaLarisa Rudenko

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