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Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations

tetano

Editor, Senior Moderator
Cell Host Microbe. 2019 Feb 6. pii: S1931-3128(19)30048-4. doi: 10.1016/j.chom.2019.01.010. [Epub ahead of print]
[h=1]Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations.[/h] Lee J[SUP]1[/SUP], Paparoditis P[SUP]2[/SUP], Horton AP[SUP]3[/SUP], Fr?hwirth A[SUP]4[/SUP], McDaniel JR[SUP]1[/SUP], Jung J[SUP]5[/SUP], Boutz DR[SUP]3[/SUP], Hussein DA[SUP]6[/SUP], Tanno Y[SUP]1[/SUP], Pappas L[SUP]4[/SUP], Ippolito GC[SUP]6[/SUP], Corti D[SUP]7[/SUP], Lanzavecchia A[SUP]2[/SUP], Georgiou G[SUP]8[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.


[h=4]KEYWORDS:[/h] anti-hemagglutinin antibodies; humoral immunity; immunological imprinting; influenza vaccine response; longitudinal profiling; persistent antibodies; serum antibody repertoire

PMID: 30795981 DOI: 10.1016/j.chom.2019.01.010
 
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