AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets

Daniel Stadlbauer,Edith Beaulieu,Leon De Waal,Florian Krammer,Raffael Nachbagauer,Albert D M E Osterhaus,Koert J Stittelaar,Bruce L Innis,Philippe Boutet,Corey P Mallett,Shirin Strohmeier,Edwin J B Veldhuis Kroeze

doi:10.1038/s41541-021-00299-3

Abstract

Human infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model. Serological analyses demonstrated that homologous hemagglutination inhibition and microneutralization antibody titers were detectable in the ferrets after the first immunization with the AS03-adjuvanted vaccines that were further boosted by the second immunization. In addition, heterologous antibody titers against older H7 subtype viruses of the North American lineage (H7N7, H7N3) and newer H7 subtype viruses of the Eurasian lineage (H7N9) were detected in the animals receiving the AS03-adjuvanted vaccines. Animals receiving two immunizations of the AS03-adjuvanted vaccines were protected from weight loss and fever in the homologous challenge study and had no detectable virus in throat or lung samples. In addition, microscopic examination post-challenge showed animals immunized with the AS03-adjuvanted vaccines had the least signs of lung injury and inflammation, consistent with the greater relative efficacy of the adjuvanted vaccines. In conclusion, this study demonstrated that the AS03-adjuvanted H7N9 vaccines elicited high levels of homologous and heterologous antibodies and protected against H7N9 virus damage post-challenge.

Highlights

Influenza viruses infect millions of people worldwide and result in ~290,000–650,000 influenza-related deaths each year[1]
The large number of human cases increased the likelihood of genetic reassortment of H7N9 viruses with human seasonal influenza viruses, which could lead to sustained human-to-human transmission[9]
Functional antibody titers specific for H7 HA were determined in hemagglutination inhibition (HI; Fig. 2) and virus neutralization assays (VN; Fig. 3) against the homologous H7N9 vaccine strain and antigenically heterologous H7N7 and H7N3 viruses, which circulated prior to the strain selected for the vaccines

Summary

Introduction

Influenza viruses infect millions of people worldwide and result in ~290,000–650,000 influenza-related deaths each year[1]. In addition to seasonally occurring human infections, zoonotic infections caused by avian influenza A viruses are a major public health concern and pose a pandemic threat. H7N9 virus strain emerged in China that caused hundreds of human infections. Highly pathogenic avian influenza (HPAI) H7N9 viruses emerged that featured a polybasic cleavage site in the hemagglutinin (HA) and were lethal for poultry[7,8]. In China, cases of people co-infected with both H7N9 and seasonal influenza virus strains have been reported during the period of overlapping seasonal and H7N9 epidemics[10]. An avian H7N2 virus caused an outbreak in cats in an animal shelter in New York that led to one human case[11]

Methods

Results

Conclusion