TY - JOUR
T1 - Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations
AU - Lee, Jiwon
AU - Paparoditis, Philipp
AU - Horton, Andrew P.
AU - Frühwirth, Alexander
AU - McDaniel, Jonathan R.
AU - Jung, Jiwon
AU - Boutz, Daniel R.
AU - Hussein, Dania A.
AU - Tanno, Yuri
AU - Pappas, Leontios
AU - Ippolito, Gregory C.
AU - Corti, Davide
AU - Lanzavecchia, Antonio
AU - Georgiou, George
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/3/13
Y1 - 2019/3/13
N2 - 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.
AB - 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.
KW - anti-hemagglutinin antibodies
KW - humoral immunity
KW - immunological imprinting
KW - influenza vaccine response
KW - longitudinal profiling
KW - persistent antibodies
KW - serum antibody repertoire
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U2 - 10.1016/j.chom.2019.01.010
DO - 10.1016/j.chom.2019.01.010
M3 - Article
C2 - 30795981
AN - SCOPUS:85062433602
SN - 1931-3128
VL - 25
SP - 367-376.e5
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -