[PDF][PDF] Persistent antibody clonotypes dominate the serum response to influenza over multiple years and repeated vaccinations

J Lee, P Paparoditis, AP Horton, A Frühwirth… - Cell host & …, 2019 - cell.com
J Lee, P Paparoditis, AP Horton, A Frühwirth, JR McDaniel, J Jung, DR Boutz, DA Hussein…
Cell host & microbe, 2019cell.com
Humans are repeatedly exposed to influenza virus via infections and vaccinations.
Understanding how multiple exposures and pre-existing immunity impact antibody
responses is essential for vaccine development. Given the recent prevalence of influenza
H1N1 A/California/7/2009 (CA09), we examined the clonal composition and dynamics of
CA09 hemagglutinin (HA)-reactive IgG repertoire over 5 years in a donor with multiple
influenza exposures. The anti-CA09 HA polyclonal response in this donor comprised 24 …
Summary
Humans are repeatedly exposed to influenza virus via infections and vaccinations. Understanding how multiple exposures and pre-existing immunity impact antibody responses is essential for vaccine development. Given the recent prevalence of influenza H1N1 A/California/7/2009 (CA09), we examined the clonal composition and dynamics of CA09 hemagglutinin (HA)-reactive IgG repertoire over 5 years in a donor with multiple influenza exposures. The anti-CA09 HA polyclonal response in this donor comprised 24 persistent antibody clonotypes, accounting for 72.6% ± 10.0% of the anti-CA09 HA repertoire over 5 years. These persistent antibodies displayed higher somatic hypermutation relative to transient serum antibodies detected at one time point. Additionally, persistent antibodies predominantly demonstrated cross-reactivity and potent neutralization toward a phylogenetically distant H5N1 A/Vietnam/1203/2004 (VT04) strain, a feature correlated with HA stem recognition. This analysis reveals how "serological imprinting" impacts responses to influenza and suggests that once elicited, cross-reactive antibodies targeting the HA stem can persist for years.
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