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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Background
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 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.

Methods
Naïve 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 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 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.
Original languageEnglish
Number of pages12
JournalInfluenza and Other Respiratory Viruses
DOIs
Publication statusPublished - 11 Aug 2020

Keywords

  • adjuvant
  • efficacy
  • ferret
  • immunopathology
  • influenza A
  • pandemic 2009 H1N1
  • vaccine

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