Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans

• Published in: Nature communications 2019-07, Vol.10 (1), p.3338-15, Article 3338
• Main Authors: Khurana, Surender, Hahn, Megan, Coyle, Elizabeth M., King, Lisa R., Lin, Tsai-Lien, Treanor, John, Sant, Andrea, Golding, Hana
• Format: Article
• Language: English
• Subjects: 13; 49; 59; 631/326/590/1883; 631/326/590/2292; 631/326/590/2294; 692/308/409; 82/1; 82/103; 82/79; Adolescent; Adult; Affinity; Antibodies; Antibodies, Viral - immunology; Antibody Affinity; Binding; Child; Child, Preschool; Domains; Female; Hemagglutination inhibition; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Humanities and Social Sciences; Humans; Immunization; Infant; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Male; Maturation; Middle Aged; multidisciplinary; Platforms; Science; Science (multidisciplinary); Strains (organisms); Vaccination; Vaccine efficacy; Vaccines; Viruses; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11296-5

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.