Abstract
Until universal influenza vaccines become available, pandemic preparedness should include developing classical vaccines against potential pandemic influenza subtypes. We here show that addition of SWE adjuvant, a squalene-in-water emulsion, to H7N9 split influenza vaccine clearly enhanced functional antibody responses in ferrets. These were cross-reactive against H7N9 strains from different lineages and newly emerged H7N9 variants. Both vaccine formulations protected in almost all cases against severe pneumonia induced by intratracheal infection of ferrets with H7N9 influenza; however, the SWE adjuvant enhanced protection against virus replication and disease. Correlation analysis and curve fitting showed that both VN- and NI-titers were better predictors for protection than HI-titers. Moreover, we show that novel algorithms can assist in better interpretation of large data sets generated in preclinical studies. Cluster analysis showed that the adjuvanted vaccine results in robust immunity and protection, whereas the response to the non-adjuvanted vaccine is heterogeneous, such that the protection balance may be more easily tipped toward severe disease. Finally, cluster analysis indicated that the dose-sparing capacity of the adjuvant is at least a factor six, which greatly increases vaccine availability in a pandemic situation.
Highlights
Since the first reported human infections with avian H7N9 influenza virus in China in 20131, the virus has been transmitted from the avian reservoir to humans in a seasonal fashion for several years, lately the virus appears quiescent[2]
When ferrets were immunized with split vaccine without adjuvant, low antibody levels were detected in all functional assays irrespective of dose, which in general declined after day 13 (Fig. 1)
The adjuvanted vaccine protected against severe pneumonia and virus replication and clinical signs, such as weight loss and fever were almost absent
Summary
Since the first reported human infections with avian H7N9 influenza virus in China in 20131, the virus has been transmitted from the avian reservoir to humans in a seasonal fashion for several years, lately the virus appears quiescent[2]. Several new strains had evolved to become highly pathogenic in poultry (HPAI)[8,10,11]. These isolates had acquired a multi-basic cleavage site in HA10,12,13 and mutations in the PB2 protein[12,14], which are associated with a wider tissue tropism and pathogenicity[15,16]
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