1. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
- Author
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Abdollah Naficy, Meagan McMahon, Emmanuel B. Walter, Jodi Feser, Florian Krammer, Disha Bhavsar, David I. Bernstein, Monica M. McNeal, Carine Claeys, Patrick C. Wilson, Alec W. Freyn, Alicia Solórzano, Veronika Chromikova, Juan Manuel Carreño, Chris Gast, Raffael Nachbagauer, Shirin Strohmeier, Peter Palese, Andres Javier, Carly M. Bliss, Jeffrey T. Guptill, Bruce L Innis, Teresa Aydillo, Daniel Stadlbauer, Adolfo García-Sastre, Marie Van der Wielen, Kaijun Jiang, Franceso Berlanda-Scorza, Lynda Coughlan, Weina Sun, Chiara Mariottini, Mohammad Amin Behzadi, and Christina Capuano
- Subjects
0301 basic medicine ,Adult ,Adolescent ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Antibodies, Viral ,General Biochemistry, Genetics and Molecular Biology ,Antigenic drift ,Virus ,Placebos ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Immunity ,Medicine ,Humans ,biology ,business.industry ,Immunogenicity ,Antigenic shift ,General Medicine ,Virology ,Vaccination ,030104 developmental biology ,Influenza Vaccines ,030220 oncology & carcinogenesis ,Inactivated vaccine ,biology.protein ,business - 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.
- Published
- 2020