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A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
by
García-Sastre, Adolfo
, Krammer, Florian
, Jiang, Kaijun
, Berlanda-Scorza, Franceso
, Gast, Christopher
, Van der Wielen, Marie
, Carreño, Juan Manuel
, Claeys, Carine
, Guptill, Jeffrey
, Capuano, Christina
, Palese, Peter
, Strohmeier, Shirin
, Nachbagauer, Raffael
, Bliss, Carly
, McNeal, Monica
, Bhavsar, Disha
, McMahon, Meagan
, Naficy, Abdollah
, Coughlan, Lynda
, Mariottini, Chiara
, Wilson, Patrick C.
, Feser, Jodi
, Chromikova, Veronika
, Freyn, Alec W.
, Innis, Bruce L.
, Sun, Weina
, Behzadi, Mohammad Amin
, Bernstein, David I.
, Javier, Andres
, Aydillo, Teresa
, Walter, Emmanuel B.
, Stadlbauer, Daniel
, Solórzano, Alicia
in
631/250/590
/ 631/326/590
/ 631/326/596
/ Adolescent
/ Adult
/ Antibodies
/ Antibodies, Viral - biosynthesis
/ Antigenic drift
/ Antigens
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Care and treatment
/ Deactivation
/ Hemagglutinin Glycoproteins, Influenza Virus - immunology
/ Hemagglutinins
/ Humans
/ Immune response
/ Immune system
/ Immunogenicity
/ Infectious Diseases
/ Influenza
/ Influenza vaccines
/ Influenza Vaccines - adverse effects
/ Influenza Vaccines - immunology
/ Metabolic Diseases
/ Molecular Medicine
/ Neurosciences
/ Orthomyxoviridae
/ Pandemics
/ Placebos
/ Prevention
/ Proteins
/ Safety
/ Testing
/ Vaccines
/ Viruses
/ Young Adult
2021
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A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
by
García-Sastre, Adolfo
, Krammer, Florian
, Jiang, Kaijun
, Berlanda-Scorza, Franceso
, Gast, Christopher
, Van der Wielen, Marie
, Carreño, Juan Manuel
, Claeys, Carine
, Guptill, Jeffrey
, Capuano, Christina
, Palese, Peter
, Strohmeier, Shirin
, Nachbagauer, Raffael
, Bliss, Carly
, McNeal, Monica
, Bhavsar, Disha
, McMahon, Meagan
, Naficy, Abdollah
, Coughlan, Lynda
, Mariottini, Chiara
, Wilson, Patrick C.
, Feser, Jodi
, Chromikova, Veronika
, Freyn, Alec W.
, Innis, Bruce L.
, Sun, Weina
, Behzadi, Mohammad Amin
, Bernstein, David I.
, Javier, Andres
, Aydillo, Teresa
, Walter, Emmanuel B.
, Stadlbauer, Daniel
, Solórzano, Alicia
in
631/250/590
/ 631/326/590
/ 631/326/596
/ Adolescent
/ Adult
/ Antibodies
/ Antibodies, Viral - biosynthesis
/ Antigenic drift
/ Antigens
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Care and treatment
/ Deactivation
/ Hemagglutinin Glycoproteins, Influenza Virus - immunology
/ Hemagglutinins
/ Humans
/ Immune response
/ Immune system
/ Immunogenicity
/ Infectious Diseases
/ Influenza
/ Influenza vaccines
/ Influenza Vaccines - adverse effects
/ Influenza Vaccines - immunology
/ Metabolic Diseases
/ Molecular Medicine
/ Neurosciences
/ Orthomyxoviridae
/ Pandemics
/ Placebos
/ Prevention
/ Proteins
/ Safety
/ Testing
/ Vaccines
/ Viruses
/ Young Adult
2021
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A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
by
García-Sastre, Adolfo
, Krammer, Florian
, Jiang, Kaijun
, Berlanda-Scorza, Franceso
, Gast, Christopher
, Van der Wielen, Marie
, Carreño, Juan Manuel
, Claeys, Carine
, Guptill, Jeffrey
, Capuano, Christina
, Palese, Peter
, Strohmeier, Shirin
, Nachbagauer, Raffael
, Bliss, Carly
, McNeal, Monica
, Bhavsar, Disha
, McMahon, Meagan
, Naficy, Abdollah
, Coughlan, Lynda
, Mariottini, Chiara
, Wilson, Patrick C.
, Feser, Jodi
, Chromikova, Veronika
, Freyn, Alec W.
, Innis, Bruce L.
, Sun, Weina
, Behzadi, Mohammad Amin
, Bernstein, David I.
, Javier, Andres
, Aydillo, Teresa
, Walter, Emmanuel B.
, Stadlbauer, Daniel
, Solórzano, Alicia
in
631/250/590
/ 631/326/590
/ 631/326/596
/ Adolescent
/ Adult
/ Antibodies
/ Antibodies, Viral - biosynthesis
/ Antigenic drift
/ Antigens
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Care and treatment
/ Deactivation
/ Hemagglutinin Glycoproteins, Influenza Virus - immunology
/ Hemagglutinins
/ Humans
/ Immune response
/ Immune system
/ Immunogenicity
/ Infectious Diseases
/ Influenza
/ Influenza vaccines
/ Influenza Vaccines - adverse effects
/ Influenza Vaccines - immunology
/ Metabolic Diseases
/ Molecular Medicine
/ Neurosciences
/ Orthomyxoviridae
/ Pandemics
/ Placebos
/ Prevention
/ Proteins
/ Safety
/ Testing
/ Vaccines
/ Viruses
/ Young Adult
2021
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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
A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
2021
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Overview
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.
New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.
Publisher
Nature Publishing Group US,Nature Publishing Group
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