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

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.

RDE Treatment Prevents Non-Specific Detection of SARS-CoV-2- and Influenza-Specific IgG Antibodies in Heat-Inactivated Serum Samples

“…Ten serum specimens collected from ferrets immunized with H3N2 LAIVs [ 45 ] were used as samples positive for influenza H3N2 IgG antibodies. The control group included serum samples from 20 naïve animals collected as part of preclinical trials of H7N9 LAIVs [ 46 ].…”

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

“…The H7N9 LAIV candidate is a 6:2 gene substitution reassortant, constructed in the Institute of Experimental Medicine (St Petersburg, Russian Federation) by classical reassortment between the human A/Hong Kong/125/2017 (H7N9) wild type virus of avian origin (H7N9 WT) (an A/Hunan/2650/2016-like virus of YRD HA lineage) [ 25 ] and A/Leningrad/134/17/57 (H2N2), an attenuated cold-adapted master donor virus (L17 MDV) in embryonated chicken eggs [ 26 ]. In brief, a vaccine candidate between L17 MDV and H7N9 WT virus was produced in specific pathogen-free embryonated eggs (VALO BioMedia GmbH, Germany) following seven rounds of selective propagation.…”

“…Currently circulating H7N9 viruses belong to two genetic hemagglutinin (HA) lineages—the Yangtze River Delta (YRD) and Pearl River Delta (PRD)—which are antigenically distinct from A/Anhui/1/2013-like viruses. Recent viruses of the YRD lineage reacted poorly with ferret antiserum derived from A/Anhui/1/2013 [ 25 ] and with human serum samples obtained in 2014–2015 from a phase I clinical trial of an A/Anhui/1/2013-based live attenuated influenza vaccine (LAIV) candidate [ 26 ].…”

“…In 2017, after analysis of H7N9 influenza activity, WHO proposed that new candidate vaccine viruses should be developed from A/Hunan/2650/2016-like (H7N9) strains of YRD HA lineage [ 25 ]. In response to this recommendation, in 2018 we developed an LAIV candidate against human A/Hong Kong/125/2017 strain of avian origin, a low-pathogenic A/Hunan/2650/2016-like virus, and studied its safety and immunogenicity in a ferret model [ 26 ]. This was the only live influenza vaccine based on the new YRD HA lineage virus to be included in the latest WHO tables on clinical evaluation of pandemic and potential pandemic influenza vaccines in August 2019 [ 24 ].…”

Immune Control of Avian Influenza Virus Infection and Its Vaccine Development

“…The availability of these vaccines will reduce mortality and morbidity in a pandemic scenario until exactly matching vaccines become accessible. These unique vaccines ideally would produce a simultaneous protection against zoonotic influenza viruses, antigenically drifted seasonal viruses and pandemic IVs [ 347 , 348 , 349 , 350 , 351 , 352 , 353 , 354 , 355 , 356 , 357 , 358 ]. There have been several attempts to create an effective universal influenza vaccination that can trigger a broadly reactive response against antigenically varied viruses.…”