Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs
Eleni Vatzia,
Katherine Feest,
Adam McNee,
Tanuja Manjegowda,
B. Veronica Carr,
Basudev Paudyal,
Tiphany Chrun,
Emmanuel A. Maze,
Amy Mccarron,
Susan Morris,
Helen E. Everett,
Ronan MacLoughlin,
Francisco J. Salguero,
Teresa Lambe,
Sarah C. Gilbert,
Elma Tchilian
Affiliations
Eleni Vatzia
The Pirbright Institute
Katherine Feest
The Pirbright Institute
Adam McNee
The Pirbright Institute
Tanuja Manjegowda
The Pirbright Institute
B. Veronica Carr
The Pirbright Institute
Basudev Paudyal
The Pirbright Institute
Tiphany Chrun
The Pirbright Institute
Emmanuel A. Maze
The Pirbright Institute
Amy Mccarron
The Pirbright Institute
Susan Morris
Nuffield Department of Medicine, University of Oxford
Helen E. Everett
Animal and Plant Health Agency-Weybridge, New Haw
Ronan MacLoughlin
Aerogen Ltd
Francisco J. Salguero
United Kingdom Health Security Agency, UKHSA-Porton Down
Teresa Lambe
Oxford Vaccine Group, Department of Paediatrics, Medical Sciences Division, University of Oxford and Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford
Sarah C. Gilbert
Nuffield Department of Medicine, University of Oxford
Abstract There is an urgent need for influenza vaccines providing broader protection that may decrease the need for annual immunization of the human population. We investigated the efficacy of heterologous prime boost immunization with chimpanzee adenovirus (ChAdOx2) and modified vaccinia Ankara (MVA) vectored vaccines, expressing conserved influenza virus nucleoprotein (NP), matrix protein 1 (M1) and neuraminidase (NA) in H1N1pdm09 pre-exposed pigs. We compared the efficacy of intra-nasal, aerosol and intra-muscular vaccine delivery against H3N2 influenza challenge. Aerosol prime boost immunization induced strong local lung T cell and antibody responses and abrogated viral shedding and lung pathology following H3N2 challenge. In contrast, intramuscular immunization induced powerful systemic responses and weak local lung responses but also abolished lung pathology and reduced viral shedding. These results provide valuable insights into the development of a broadly protective influenza vaccine in a highly relevant large animal model and will inform future vaccine and clinical trial design.
