Inactivated pandemic 2009 H1N1 influenza A virus human vaccines have different efficacy after homologous challenge in the ferret model.

Beatriz Vidaña,Maria Zambon,Helen E Everett,Othmar Engelhardt,Diane Major,Katja Hoschler,Ian H Brown,Sharon M Brookes,Alejandro Nuñez,Fanny Garcon

doi:10.1111/irv.12784

Abstract

BackgroundThe 2009 pandemic H1N1 (A(H1N1)pdm09) influenza A virus (IAV) has replaced the previous seasonal H1N1 strain in humans and continues to circulate worldwide. The comparative performance of inactivated A(H1N1)pdm09 influenza vaccines remains of considerable interest. The objective of this study was to evaluate the efficacy of two licensed A(H1N1)pdm09 inactivated vaccines (AS03B adjuvanted split virion Pandemrix from GlaxoSmithKline and referred here as (V1) and non‐adjuvanted whole virion Celvapan from Baxter and referred here as (V2)) in ferrets as a pre‐clinical model for human disease intervention.MethodsNaïve ferrets were divided into two groups (V1 and V2) and immunised intramuscularly with two different A/California/07/2009‐derived inactivated vaccines, V1 administered in a single dose and V2 administered in 2 doses separated by 21 days. Six weeks after the first immunisation, vaccinated animals and a non‐vaccinated control (NVC) group were intra‐nasally challenged with 106.5 TCID50 of the isolate A/England/195/2009 A(H1N1)pdm09 with 99.1% amino acid identity to the vaccine strain. Clinical signs, lung histopathology, viral quantification and antibody responses were evaluated.Results and ConclusionsResults revealed important qualitative differences in the performance of both inactivated vaccines in relation to protection against challenge with a comparable virus in a naive animal (ferret) model of human disease. Vaccine V1 limited and controlled viral shedding and reduced lower respiratory tract infection. In contrast, vaccine V2 did not control infection and animals showed sustained viral shedding and delayed lower respiratory infection, resulting in pulmonary lesions, suggesting lower efficacy of V2 vaccine.

Highlights

The 2009 pandemic H1N1 (A(H1N1)pdm09) influenza A virus (IAV) has replaced the previous seasonal H1N1 strain in humans and continues to circulate worldwide
This study evaluates the efficacy of two A(H1N1)pdm09-derived inactivated vaccines, one adjuvanted Pandemrix (AS03B adjuvanted split virion vaccine) referred hereafter as Vaccine 1 (V1) and one non-adjuvanted Celvapan referred hereafter as Vaccine 2 (V2) at the human dose and schedule[6] in the ferret (Mustela putorius furo) model after challenge with a A(H1N1)pdm[09] strain
Vaccine 1 (V1) was a split inactivated influenza virus vaccine constructed from the vlike strain antigen (New York Medical College x-179A), generated by classical re-assortment in embryonated eggs consisting of a 0.25 mL suspension containing 3.75 μg of HA mixed with 0.25 mL emulsion of AS03B adjuvant and the latter composed of squalene (10.69 mg), DL-α-tocopherol (11.86 mg) and polysorbate 80 (4.86 mg)

Summary

Introduction

The 2009 pandemic H1N1 (A(H1N1)pdm09) influenza A virus (IAV) has replaced the previous seasonal H1N1 strain in humans and continues to circulate worldwide. The objective of this study was to evaluate the efficacy of two licensed A(H1N1)pdm[09] inactivated vaccines (AS03B adjuvanted split virion Pandemrix from GlaxoSmithKline and referred here as (V1) and non-adjuvanted whole virion Celvapan from Baxter and referred here as (V2)) in ferrets as a pre-clinical model for human disease intervention. Six weeks after the first immunisation, vaccinated animals and a non-vaccinated control (NVC) group were intra-nasally challenged with 106.5 TCID50 of the isolate A/England/195/2009 A(H1N1)pdm[09] with 99.1% amino acid identity to the vaccine strain. Results and Conclusions: Results revealed important qualitative differences in the performance of both inactivated vaccines in relation to protection against challenge with a comparable virus in a naive animal (ferret) model of human disease. Vaccine V2 did not control infection and animals showed sustained viral shedding and delayed lower respiratory infection, resulting in pulmonary lesions, suggesting lower efficacy of V2 vaccine

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