TY - JOUR

T1 - Two live attenuated vaccines against recent low–and highly pathogenic H7N9 influenza viruses are safe and immunogenic in ferrets

AU - Rudenko, Larisa

AU - Kiseleva, Irina

AU - Krutikova, Elena

AU - Stepanova, Ekaterina

AU - Isakova-Sivak, Irina

AU - Donina, Svetlana

AU - Rekstin, Andrey

AU - Pisareva, Maria

AU - Bazhenova, Ekaterina

AU - Kotomina, Tatiana

AU - Katelnikova, Anastasia

AU - Muzhikyan, Arman

AU - Makarov, Valery

AU - Sparrow, Erin Grace

AU - Torelli, Guido

N1 - Funding Information: Funding: Development of live attenuated vaccine based on A/Hong Kong/125/2017 (H7N9) influenza virus was funded by WHO, grant number TTI-LOA17-IEM-1. Publisher Copyright: © 2018 by the World Health Organization.Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/12

Y1 - 2018/12

N2 - Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virological and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused the majority of human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial.

AB - Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virological and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused the majority of human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial.

KW - Avian influenza

KW - H7N9

KW - Live attenuated influenza vaccine

KW - Pandemic threat

UR - http://www.scopus.com/inward/record.url?scp=85056656137&partnerID=8YFLogxK

U2 - 10.3390/vaccines6040074

DO - 10.3390/vaccines6040074

M3 - Article

AN - SCOPUS:85056656137

VL - 6

JO - Vaccines

JF - Vaccines

SN - 2076-393X

IS - 4

M1 - 74

ER -