Quadrivalent influenza nanoparticle vaccines induce broad protection

Seyhan Boyoglu-Barnum, Daniel Ellis, Rebecca A. Gillespie, Geoffrey B. Hutchinson, Young-Jun Park, Syed M. Moin, Oliver J. Acton, Rashmi Ravichandran, Mike Murphy, Deleah Pettie, Nick Matheson, Lauren Carter, Adrian Creanga, Michael J. Watson, Sally Kephart, Sila Ataca, John R. Vaile, George Ueda, Michelle C. Crank, Lance Stewart, Kelly K. Lee, Miklos Guttman, David Baker, John R. Mascola, David Veesler, Barney S. Graham (), Neil P. King () and Masaru Kanekiyo ()
Additional contact information
Seyhan Boyoglu-Barnum: National Institutes of Health
Daniel Ellis: University of Washington
Rebecca A. Gillespie: National Institutes of Health
Geoffrey B. Hutchinson: National Institutes of Health
Young-Jun Park: University of Washington
Syed M. Moin: National Institutes of Health
Oliver J. Acton: University of Washington
Rashmi Ravichandran: University of Washington
Mike Murphy: University of Washington
Deleah Pettie: University of Washington
Nick Matheson: University of Washington
Lauren Carter: University of Washington
Adrian Creanga: National Institutes of Health
Michael J. Watson: University of Washington
Sally Kephart: University of Washington
Sila Ataca: National Institutes of Health
John R. Vaile: National Institutes of Health
George Ueda: University of Washington
Michelle C. Crank: National Institutes of Health
Lance Stewart: University of Washington
Kelly K. Lee: University of Washington
Miklos Guttman: University of Washington
David Baker: University of Washington
John R. Mascola: National Institutes of Health
David Veesler: University of Washington
Barney S. Graham: National Institutes of Health
Neil P. King: University of Washington
Masaru Kanekiyo: National Institutes of Health

Nature, 2021, vol. 592, issue 7855, 623-628

Abstract: Abstract Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization1. Here we show that computationally designed, two-component nanoparticle immunogens2 induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines3.

Date: 2021
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DOI: 10.1038/s41586-021-03365-x

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