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

Jiwon Lee; Philipp Paparoditis; Andrew P. Horton; Alexander Frühwirth; Jonathan R. McDaniel; Jiwon Jung; Daniel R. Boutz; Dania A. Hussein; Yuri Tanno; Leontios Pappas; Gregory C. Ippolito; Davide Corti; Antonio Lanzavecchia; George Georgiou

doi:10.1016/j.chom.2019.01.010

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

Jiwon Lee, Philipp Paparoditis, Andrew P. Horton, Alexander Frühwirth, Jonathan R. McDaniel, Jiwon Jung, Daniel R. Boutz, Dania A. Hussein, Yuri Tanno, Leontios Pappas, Gregory C. Ippolito, Davide Corti, Antonio Lanzavecchia, George Georgiou

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50 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	367-376.e5
Journal	Cell Host and Microbe
Volume	25
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2019.01.010
State	Published - Mar 13 2019

Keywords

anti-hemagglutinin antibodies
humoral immunity
immunological imprinting
influenza vaccine response
longitudinal profiling
persistent antibodies
serum antibody repertoire

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2019.01.010

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Lee, J., Paparoditis, P., Horton, A. P., Frühwirth, A., McDaniel, J. R., Jung, J., Boutz, D. R., Hussein, D. A., Tanno, Y., Pappas, L., Ippolito, G. C., Corti, D., Lanzavecchia, A., & Georgiou, G. (2019). Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations. Cell Host and Microbe, 25(3), 367-376.e5. https://doi.org/10.1016/j.chom.2019.01.010

Lee, J, Paparoditis, P, Horton, AP, Frühwirth, A, McDaniel, JR, Jung, J, Boutz, DR, Hussein, DA, Tanno, Y, Pappas, L, Ippolito, GC, Corti, D, Lanzavecchia, A & Georgiou, G 2019, 'Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations', Cell Host and Microbe, vol. 25, no. 3, pp. 367-376.e5. https://doi.org/10.1016/j.chom.2019.01.010

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title = "Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations",

abstract = "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.",

keywords = "anti-hemagglutinin antibodies, humoral immunity, immunological imprinting, influenza vaccine response, longitudinal profiling, persistent antibodies, serum antibody repertoire",

author = "Jiwon Lee and Philipp Paparoditis and Horton, {Andrew P.} and Alexander Fr{\"u}hwirth and McDaniel, {Jonathan R.} and Jiwon Jung and Boutz, {Daniel R.} and Hussein, {Dania A.} and Yuri Tanno and Leontios Pappas and Ippolito, {Gregory C.} and Davide Corti and Antonio Lanzavecchia and George Georgiou",

note = "Funding Information: We are grateful to Dr. Sebastian Sch{\"a}tzle 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 Sch{\"a}tzle 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: {\textcopyright} 2019 Elsevier Inc.",

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doi = "10.1016/j.chom.2019.01.010",

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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

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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.

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

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