Two Live Attenuated Vaccines against Recent Low⁻and Highly Pathogenic H7N9 Influenza Viruses Are Safe and Immunogenic in Ferrets.

Larisa Rudenko,Tatiana Kotomina,Irina Isakova-Sivak,Erin Sparrow,Guido Torelli,Anastasia Katelnikova,Ekaterina Stepanova,Ekaterina Bazhenova,Valery Makarov,Elena Krutikova,Andrey Rekstin,Maria Pisareva,Svetlana Donina,Arman Muzhikyan,Irina Kiseleva

doi:10.3390/vaccines6040074

Larisa Rudenko, Tatiana Kotomina + Show 13 more

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https://doi.org/10.3390/vaccines6040074

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Abstract

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.

Highlights

Since 1958, when the first human infection with a zoonotic influenza A virus was serologically confirmed [1], a number of different subtypes of animal and avian influenza A virus have infected humans [2]
The current study aimed to develop live attenuated influenza vaccine (LAIV) candidates based on currently circulating low pathogenic (A/HK) and highly pathogenic (A/GD) H7N9 avian influenza viruses, and to confirm their safety and immunogenicity in preclinical studies in a ferret model, with a view to choosing the most promising one for a phase I clinical trial
master donor virus (MDV); all rights on the Len/17 belong to the Institute of Experimental Medicine (IEM), St Petersburg, Russia. (ii) A/Hong Kong/125/2017 (H7N9) avian influenza virus was provided by Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA. (iii) A/17/HK LAIV candidate was developed by classical reassortment of

Summary

Introduction

Since 1958, when the first human infection with a zoonotic influenza A virus was serologically confirmed [1], a number of different subtypes of animal and avian influenza A virus have infected humans [2]. The spread of these viruses in bird populations, the likelihood of reassortment with other influenza viruses of birds and mammals, the proven transmission from birds to humans, and the high case-fatality rate (CFR) among infected people have raised significant concerns for global public health. Using an Influenza Risk Assessment Tool (IRAT), the Centers for Disease Control and Prevention (CDC) rated the H7N9 (A/Hong Kong/125/2017) virus as having the highest pandemic emergence and impact scores among all potentially pandemic viruses evaluated [9]

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