Sequential vaccinations with divergent H1N1 influenza virus strains induce multi-H1 clade neutralizing antibodies in swine

Kristien Reeth (), Anna Parys, José Carlos Mancera Gracia, Ivan Trus, Koen Chiers, Philip Meade, Sean Liu, Peter Palese, Florian Krammer and Elien Vandoorn
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Kristien Reeth: Ghent University
Anna Parys: Ghent University
José Carlos Mancera Gracia: Ghent University
Ivan Trus: International Institute of Molecular and Cell Biology
Koen Chiers: Ghent University
Philip Meade: Icahn School of Medicine at Mount Sinai
Sean Liu: Icahn School of Medicine at Mount Sinai
Peter Palese: Icahn School of Medicine at Mount Sinai
Florian Krammer: Icahn School of Medicine at Mount Sinai
Elien Vandoorn: Ghent University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Vaccines that protect against any H1N1 influenza A virus strain would be advantageous for use in pigs and humans. Here, we try to induce a pan-H1N1 antibody response in pigs by sequential vaccination with antigenically divergent H1N1 strains. Adjuvanted whole inactivated vaccines are given intramuscularly in various two- and three-dose regimens. Three doses of heterologous monovalent H1N1 vaccine result in seroprotective neutralizing antibodies against 71% of a diverse panel of human and swine H1 strains, detectable antibodies against 88% of strains, and sterile cross-clade immunity against two heterologous challenge strains. This strategy outperforms any two-dose regimen and is as good or better than giving three doses of matched trivalent vaccine. Neutralizing antibodies are H1-specific, and the second heterologous booster enhances reactivity with conserved epitopes in the HA head. We show that even the most traditional influenza vaccines can offer surprisingly broad protection if they are administered in an alternative way.

Date: 2023
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DOI: 10.1038/s41467-023-43339-3

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