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, Jodi Feser, Abdollah Naficy, David I. Bernstein, Jeffrey Guptill, Emmanuel B. Walter, Franceso Berlanda-Scorza, Daniel Stadlbauer, Patrick C. Wilson, Teresa Aydillo, Mohammad Amin Behzadi, Disha Bhavsar, Carly Bliss, Christina Capuano, Juan Manuel Carreño, Veronika Chromikova, Carine Claeys, Lynda Coughlan, Alec W. Freyn, Christopher GastAndres Javier, Kaijun Jiang, Chiara Mariottini, Meagan McMahon, Monica McNeal, Alicia Solórzano, Shirin Strohmeier, Weina Sun, Marie Van der Wielen, Bruce L. Innis, Adolfo García-Sastre, Peter Palese, Florian Krammer

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

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.

Original languageEnglish
Pages (from-to)106-114
Number of pages9
JournalNature Medicine
Volume27
Issue number1
DOIs
StatePublished - Jan 2021

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