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 journalArticlepeer-review

3 Citations (Scopus)

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
Pages (from-to)142-153
Number of pages12
JournalInfluenza and other Respiratory Viruses
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
This project was accomplished by the Pandemic Influenza Vaccine Evaluation Consortium (PIVEC), which was established as a consortium of HPA/PHE (Colindale and NIBSC) and VLA/AHVLA/APHA . The members would like to thank Elizabeth Millar and John Wood for their invaluable input at the outset of the project, funded by NIHR—Department of Health Policy Research Programme Central Commissioning Facility (PRP CCF) grant number 019/0030. APHA core staff are supported by DEFRA (England) and the devolved administrations in Scotland and Wales. The authors are grateful to Lorenzo Rapisarda (Named Veterinary Surgeon); Rachel Baker, Kevin Furey, Paul Sharp, Stuart Smith and Marie Rickard (Animal Services Unit, APHA); Kate Guilfoyle, Rose Leahy, Pauline Lloyd and Sarah Skeldon (NIBSC); Nichola Goddard (HPA); and Virag Patel (Statistical Analysis, APHA) for their service and advice.

Funding Information:
This project was accomplished by the Pandemic Influenza Vaccine Evaluation Consortium (PIVEC), which was established as a consortium of HPA/PHE (Colindale and NIBSC) and VLA/AHVLA/APHA. The members would like to thank Elizabeth Millar and John Wood for their invaluable input at the outset of the project, funded by NIHR?Department of Health Policy Research Programme Central Commissioning Facility (PRP CCF) grant number 019/0030. APHA core staff are supported by DEFRA (England) and the devolved administrations in Scotland and Wales. The authors are grateful to Lorenzo Rapisarda (Named Veterinary Surgeon); Rachel Baker, Kevin Furey, Paul Sharp, Stuart Smith and Marie Rickard (Animal Services Unit, APHA); Kate Guilfoyle, Rose Leahy, Pauline Lloyd and Sarah Skeldon (NIBSC); Nichola Goddard (HPA); and Virag Patel (Statistical Analysis, APHA) for their service and advice.

Keywords

  • IMMUNOGENICITY
  • INFECTION
  • PATHOGENESIS
  • adjuvant
  • efficacy
  • ferret
  • immunopathology
  • influenza A
  • vaccine

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