BACKGROUND: The H1N1 2009 influenza (H1N1pdm09) pandemic had unexpected features, including lower morbidity and mortality in elderly populations. METHODS: We performed in-depth elucidation of antibody responses generated post-H1N1pdm09 vaccination in elderly (aged 66-83 years) and younger (aged 18-45 or 46-65 years) adults using H1N1pdm09 whole-genome-fragment phage display library and measured antibody isotype and affinity to antigenic domains within hemagglutinin (HA). RESULTS: H1N1pdm09 vaccination induced 10-fold higher antibody levels in elderly compared with younger adults. These antibodies primarily targeted the HA1 globular domain, including neutralizing epitopes in the receptor-binding domain. Antibody epitope repertoire, isotype, and affinity maturation after H1N1pdm09 vaccination evolved independently for HA2, HA1, and HA1 N-terminus antigenic regions. Postvaccination serum samples from elderly subjects demonstrated substantially higher avidity than from younger subjects (>60% vs <30% resistance to 7 mol/L urea) and slower antibody dissociation rates using surface plasmon resonance. We also identified a gender difference in postvaccination antibody avidity (female < male subjects) in adults <65 years old. CONCLUSIONS: This is the first study in humans that provides evidence for a qualitatively superior antibody response in elderly adults after H1N1pdm09 vaccination. These findings may help explain the age-related mortality observed during the H1N1pdm09 pandemic. The difference in gender specific avidity merits further exploration.
BACKGROUND: The H1N1 2009 influenza (H1N1pdm09) pandemic had unexpected features, including lower morbidity and mortality in elderly populations. METHODS: We performed in-depth elucidation of antibody responses generated post-H1N1pdm09 vaccination in elderly (aged 66-83 years) and younger (aged 18-45 or 46-65 years) adults using H1N1pdm09 whole-genome-fragment phage display library and measured antibody isotype and affinity to antigenic domains within hemagglutinin (HA). RESULTS: H1N1pdm09 vaccination induced 10-fold higher antibody levels in elderly compared with younger adults. These antibodies primarily targeted the HA1 globular domain, including neutralizing epitopes in the receptor-binding domain. Antibody epitope repertoire, isotype, and affinity maturation after H1N1pdm09 vaccination evolved independently for HA2, HA1, and HA1 N-terminus antigenic regions. Postvaccination serum samples from elderly subjects demonstrated substantially higher avidity than from younger subjects (>60% vs <30% resistance to 7 mol/L urea) and slower antibody dissociation rates using surface plasmon resonance. We also identified a gender difference in postvaccination antibody avidity (female < male subjects) in adults <65 years old. CONCLUSIONS: This is the first study in humans that provides evidence for a qualitatively superior antibody response in elderly adults after H1N1pdm09 vaccination. These findings may help explain the age-related mortality observed during the H1N1pdm09 pandemic. The difference in gender specific avidity merits further exploration.
Authors: Brenda L Tesini; Preshetha Kanagaiah; Jiong Wang; Megan Hahn; Jessica L Halliley; Francisco A Chaves; Phuong Q T Nguyen; Aitor Nogales; Marta L DeDiego; Christopher S Anderson; Ali H Ellebedy; Shirin Strohmeier; Florian Krammer; Hongmei Yang; Sanjukta Bandyopadhyay; Rafi Ahmed; John J Treanor; Luis Martinez-Sobrido; Hana Golding; Surender Khurana; Martin S Zand; David J Topham; Mark Y Sangster Journal: J Virol Date: 2019-04-03 Impact factor: 5.103
Authors: Mark Y Sangster; Jane Baer; Felix W Santiago; Theresa Fitzgerald; Natalia A Ilyushina; Aarthi Sundararajan; Alicia D Henn; Florian Krammer; Hongmei Yang; Catherine J Luke; Martin S Zand; Peter F Wright; John J Treanor; David J Topham; Kanta Subbarao Journal: Clin Vaccine Immunol Date: 2013-04-10