TY - JOUR
T1 - Immune response following H1N1pdm09 vaccination
T2 - Differences in antibody repertoire and avidity in young adults and elderly populations stratified by age and gender
AU - Khurana, Surender
AU - Verma, Nitin
AU - Talaat, Kawsar R.
AU - Karron, Ruth A.
AU - Golding, Hana
N1 - Funding Information:
Financial support. This work was supported by Food and Drug Administration Pandemic Flu Preparedness funds (H. G).
Funding Information:
Potential conflicts of interest. The original clinical trial from which serum specimens were obtained was sponsored by CSL Limited. R. A. K. has received research support from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); has served as a consultant to or member of a scientific advisory board for Novartis, Novavax, and GlaxoSmithKline; and has served as a member of a data and safety monitoring board for GlaxoSmithKline. K. R. T. has received research support from NIAID, NIH. All other authors report no potential conflicts.
PY - 2012/2/15
Y1 - 2012/2/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir791
DO - 10.1093/infdis/jir791
M3 - Article
C2 - 22207649
AN - SCOPUS:84856297845
SN - 0022-1899
VL - 205
SP - 610
EP - 620
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -