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 - Funding Information:
We are grateful to Dr. Sebastian Schätzle and Dr. Yariv Wine for discussion and advice and Dr. Stephen Harrison and Dr. Aaron Schmidt (Harvard Medical School) for insightful discussions and providing rHA. This work was supported by NIH grant P01 AI089618 (G.G.), DTRA contract HDTRA1-12-C-0105 (G.G.), Clayton Foundation (G.G.), and European Research Council (grant no. 670955) BROADimmune (A.L.).
Funding Information:
We are grateful to Dr. Sebastian Schätzle and Dr. Yariv Wine for discussion and advice and Dr. Stephen Harrison and Dr. Aaron Schmidt (Harvard Medical School) for insightful discussions and providing rHA. This work was supported by NIH grant P01 AI089618 (G.G.), DTRA contract HDTRA1-12-C-0105 (G.G.), Clayton Foundation (G.G.), and European Research Council (grant no. 670955 ) BROADimmune (A.L.).
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
VL - 25
SP - 367-376.e5
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 3
ER -