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Clinical Trial
. 2021 Jan;27(1):106-114.
doi: 10.1038/s41591-020-1118-7. Epub 2020 Dec 7.

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Raffael Nachbagauer  1   2 , Jodi Feser  3 , Abdollah Naficy  3 , David I Bernstein  4   5 , Jeffrey Guptill  6 , Emmanuel B Walter  6   7 , Franceso Berlanda-Scorza  3   8 , Daniel Stadlbauer  1 , Patrick C Wilson  9   10 , Teresa Aydillo  1   11 , Mohammad Amin Behzadi  1 , Disha Bhavsar  1 , Carly Bliss  1 , Christina Capuano  1 , Juan Manuel Carreño  1 , Veronika Chromikova  1 , Carine Claeys  12   13 , Lynda Coughlan  1 , Alec W Freyn  1   14 , Christopher Gast  3 , Andres Javier  1 , Kaijun Jiang  1 , Chiara Mariottini  1 , Meagan McMahon  1 , Monica McNeal  4   5 , Alicia Solórzano  1   15 , Shirin Strohmeier  1   16 , Weina Sun  1 , Marie Van der Wielen  12 , Bruce L Innis  3 , Adolfo García-Sastre  1   11   17   18 , Peter Palese  1   17   18 , Florian Krammer  19
Affiliations

Affiliations

  • 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 2 Moderna, Cambridge, MA, USA.
  • 3 Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.
  • 4 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • 5 Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 6 Duke Early Phase Clinical Research Unit, Duke Clinical Research Institute, Durham, NC, USA.
  • 7 Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • 8 GSK, Siena, Italy.
  • 9 Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • 10 The Committee on Immunology, University of Chicago, Chicago, IL, USA.
  • 11 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 12 GSK, Wavre, Belgium.
  • 13 Spmt-Arista Asbl, Brussels, Belgium.
  • 14 Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 15 Pfizer, Pearl River, NY, USA.
  • 16 Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
  • 17 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 18 The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 19 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. florian.krammer@mssm.edu.
Clinical Trial

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Raffael Nachbagauer et al. Nat Med. 2021 Jan.
. 2021 Jan;27(1):106-114.
doi: 10.1038/s41591-020-1118-7. Epub 2020 Dec 7.

Authors

Raffael Nachbagauer  1   2 , Jodi Feser  3 , Abdollah Naficy  3 , David I Bernstein  4   5 , Jeffrey Guptill  6 , Emmanuel B Walter  6   7 , Franceso Berlanda-Scorza  3   8 , Daniel Stadlbauer  1 , Patrick C Wilson  9   10 , Teresa Aydillo  1   11 , Mohammad Amin Behzadi  1 , Disha Bhavsar  1 , Carly Bliss  1 , Christina Capuano  1 , Juan Manuel Carreño  1 , Veronika Chromikova  1 , Carine Claeys  12   13 , Lynda Coughlan  1 , Alec W Freyn  1   14 , Christopher Gast  3 , Andres Javier  1 , Kaijun Jiang  1 , Chiara Mariottini  1 , Meagan McMahon  1 , Monica McNeal  4   5 , Alicia Solórzano  1   15 , Shirin Strohmeier  1   16 , Weina Sun  1 , Marie Van der Wielen  12 , Bruce L Innis  3 , Adolfo García-Sastre  1   11   17   18 , Peter Palese  1   17   18 , Florian Krammer  19

Affiliations

  • 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 2 Moderna, Cambridge, MA, USA.
  • 3 Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.
  • 4 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • 5 Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 6 Duke Early Phase Clinical Research Unit, Duke Clinical Research Institute, Durham, NC, USA.
  • 7 Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • 8 GSK, Siena, Italy.
  • 9 Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • 10 The Committee on Immunology, University of Chicago, Chicago, IL, USA.
  • 11 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 12 GSK, Wavre, Belgium.
  • 13 Spmt-Arista Asbl, Brussels, Belgium.
  • 14 Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 15 Pfizer, Pearl River, NY, USA.
  • 16 Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
  • 17 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 18 The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 19 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. florian.krammer@mssm.edu.

Abstract

Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

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References

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