Immune Response Following H1N1pdm09 Vaccination: Differences in Antibody Repertoire and Avidity in Young Adults and Elderly Populations Stratified by Age and Gender

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.