Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins

• Published in: Nature immunology Vol. 18; no. 4; pp. 464 - 473
• Main Authors: Nachbagauer, Raffael, Choi, Angela, Hirsh, Ariana, Margine, Irina, Iida, Sayaka, Barrera, Aldo, Ferres, Marcela, Albrecht, Randy A, García-Sastre, Adolfo, Bouvier, Nicole M, Ito, Kimihito, Medina, Rafael A, Palese, Peter, Krammer, Florian
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2017; Nature Publishing Group
• Subjects: 631/250/2152/2153/1291; 631/326/596/1578; 64; 64/60; 692/699/255/2514; 82; 82/80; Adolescent; Adult; Age Factors; Animal models; Animals; Antibodies; Antibodies, Viral - immunology; Antigen-antibody reactions; Antigenic drift; Biomedicine; Cluster Analysis; Cross Reactions - immunology; Cross-reactivity; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Epitopes; Exo-a-sialidase; Female; Ferrets; Genetic aspects; Glycoproteins; Guinea Pigs; Health aspects; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Humans; Immune imprinting; Immunoglobulin G - immunology; Immunology; Infectious Diseases; Influenza; Influenza A virus - classification; Influenza A virus - immunology; Influenza viruses; Influenza, Human - immunology; Male; Mice; Middle Aged; Mustela; Neuraminidase - immunology; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Pandemics; resource; Viral Envelope Proteins - immunology; Viral Proteins - immunology; Virulence (Microbiology); Viruses; Young Adult
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.3684

Antigenic drift and reassortment alters the epitopes of influenza virus. Krammer and colleagues reveal the cross-reactivity of antibody responses to viral hemagglutinin and neuraminidase in humans and several animal models, but the most prominent responses reflect ‘original antigenic sin’ to viral exposure. Infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. To assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent H1N1 or H3N2 subtypes of influenza virus. We measured antibody responses by ELISA of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. Guinea pigs developed high titers of broadly cross-reactive antibodies; mice and ferrets exhibited narrower humoral responses. Then, we compared antibody responses after infection of humans with influenza virus H1N1 or H3N2 and found markedly broad responses and cogent evidence for 'original antigenic sin'. This work will inform the design of universal vaccines against influenza virus and can guide pandemic-preparedness efforts directed against emerging influenza viruses.