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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Nachbagauer, R; Feser, J; Naficy, A; Bernstein, DI; Guptill, J; Walter, EB; Berlanda-Scorza, F; Stadlbauer, D; Wilson, PC; Aydillo, T; Behzadi, MA; Bhavsar, D; Bliss, C; Capuano, C; Carreño, JM; Chromikova, V; Claeys, C; Coughlan, L; Freyn, AW; Gast, C; Javier, A; Jiang, K; Mariottini, C; McMahon, M; McNeal, M; Solórzano, A; Strohmeier, S; Sun, W; Van der Wielen, M; Innis, BL; García-Sastre, A; Palese, P; Krammer, F

Published Date

  • January 2021

Published In

Volume / Issue

  • 27 / 1

Start / End Page

  • 106 - 114

PubMed ID

  • 33288923

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-020-1118-7


  • eng

Conference Location

  • United States