Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.
Identifieur interne : 000F94 ( Main/Exploration ); précédent : 000F93; suivant : 000F95Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.
Auteurs : Marios Koutsakos [Australie] ; Adam K. Wheatley [Australie] ; Liyen Loh [Australie] ; E Bridie Clemens [Australie] ; Sneha Sant [Australie] ; Simone Nüssing [Australie] ; Annette Fox [Australie] ; Amy W. Chung [Australie] ; Karen L. Laurie [Australie] ; Aeron C. Hurt [Australie] ; Steve Rockman [Australie] ; Martha Lappas [Australie] ; Thomas Loudovaris [Australie] ; Stuart I. Mannering [Australie] ; Glen P. Westall [Australie] ; Michael Elliot [Australie] ; Stuart G. Tangye [Australie] ; Linda M. Wakim [Australie] ; Stephen J. Kent [Australie] ; Thi H O. Nguyen [Australie] ; Katherine Kedzierska [Australie]Source :
- Science translational medicine [ 1946-6242 ] ; 2018.
Descripteurs français
- KwdFr :
- Adulte (MeSH), Anticorps antiviraux (immunologie), Antigènes CD (métabolisme), Cellules productrices d'anticorps (métabolisme), Glycoprotéine hémagglutinine du virus influenza (métabolisme), Grippe humaine (immunologie), Grippe humaine (sang), Humains (MeSH), Immunité cellulaire (MeSH), Lymphocytes B (immunologie), Lymphocytes T auxiliaires (immunologie), Mémoire immunologique (MeSH), Vaccination (MeSH), Vaccins inactivés (immunologie).
- MESH :
- immunologie : Anticorps antiviraux, Grippe humaine, Lymphocytes B, Lymphocytes T auxiliaires, Vaccins inactivés.
- métabolisme : Antigènes CD, Cellules productrices d'anticorps, Glycoprotéine hémagglutinine du virus influenza.
- sang : Grippe humaine.
- Adulte, Humains, Immunité cellulaire, Mémoire immunologique, Vaccination.
English descriptors
- KwdEn :
- Adult (MeSH), Antibodies, Viral (immunology), Antibody-Producing Cells (metabolism), Antigens, CD (metabolism), B-Lymphocytes (immunology), Hemagglutinin Glycoproteins, Influenza Virus (metabolism), Humans (MeSH), Immunity, Cellular (MeSH), Immunologic Memory (MeSH), Influenza, Human (blood), Influenza, Human (immunology), T-Lymphocytes, Helper-Inducer (immunology), Vaccination (MeSH), Vaccines, Inactivated (immunology).
- MESH :
- chemical , immunology : Antibodies, Viral, Vaccines, Inactivated.
- blood : Influenza, Human.
- immunology : B-Lymphocytes, Influenza, Human, T-Lymphocytes, Helper-Inducer.
- metabolism : Antibody-Producing Cells, Antigens, CD, Hemagglutinin Glycoproteins, Influenza Virus.
- Adult, Humans, Immunity, Cellular, Immunologic Memory, Vaccination.
Abstract
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (TFH) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5-CXCR3+ antibody-secreting B cell population, CD21hiCD27+ memory B cells, and CD21loCD27+ B cells. Activation of circulating TFH cells correlated with the development of both CD21lo and CD21hi memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8+, mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21hiCD27+) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating TFH cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.
DOI: 10.1126/scitranslmed.aan8405
PubMed: 29444980
Affiliations:
- Australie
- Nouvelle-Galles du Sud, Victoria (État)
- Melbourne, Sydney
- Université de Melbourne, Université de Sydney
Links toward previous steps (curation, corpus...)
Le document en format XML
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<author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G" last="Tangye">Stuart G. Tangye</name>
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<author><name sortKey="Wakim, Linda M" sort="Wakim, Linda M" uniqKey="Wakim L" first="Linda M" last="Wakim">Linda M. Wakim</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
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<author><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004</wicri:regionArea>
<wicri:noRegion>Victoria 3004</wicri:noRegion>
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<affiliation wicri:level="4"><nlm:affiliation>ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
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<author><name sortKey="Nguyen, Thi H O" sort="Nguyen, Thi H O" uniqKey="Nguyen T" first="Thi H O" last="Nguyen">Thi H O. Nguyen</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
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<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Circulating T<sub>FH</sub>
cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.</title>
<author><name sortKey="Koutsakos, Marios" sort="Koutsakos, Marios" uniqKey="Koutsakos M" first="Marios" last="Koutsakos">Marios Koutsakos</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K" last="Wheatley">Adam K. Wheatley</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loh, Liyen" sort="Loh, Liyen" uniqKey="Loh L" first="Liyen" last="Loh">Liyen Loh</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Clemens, E Bridie" sort="Clemens, E Bridie" uniqKey="Clemens E" first="E Bridie" last="Clemens">E Bridie Clemens</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sant, Sneha" sort="Sant, Sneha" uniqKey="Sant S" first="Sneha" last="Sant">Sneha Sant</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nussing, Simone" sort="Nussing, Simone" uniqKey="Nussing S" first="Simone" last="Nüssing">Simone Nüssing</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fox, Annette" sort="Fox, Annette" uniqKey="Fox A" first="Annette" last="Fox">Annette Fox</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chung, Amy W" sort="Chung, Amy W" uniqKey="Chung A" first="Amy W" last="Chung">Amy W. Chung</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Laurie, Karen L" sort="Laurie, Karen L" uniqKey="Laurie K" first="Karen L" last="Laurie">Karen L. Laurie</name>
<affiliation wicri:level="1"><nlm:affiliation>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000</wicri:regionArea>
<wicri:noRegion>Victoria 3000</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hurt, Aeron C" sort="Hurt, Aeron C" uniqKey="Hurt A" first="Aeron C" last="Hurt">Aeron C. Hurt</name>
<affiliation wicri:level="1"><nlm:affiliation>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000</wicri:regionArea>
<wicri:noRegion>Victoria 3000</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rockman, Steve" sort="Rockman, Steve" uniqKey="Rockman S" first="Steve" last="Rockman">Steve Rockman</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Seqirus, 63 Poplar Road, Parkville, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Seqirus, 63 Poplar Road, Parkville, Victoria 3052</wicri:regionArea>
<wicri:noRegion>Victoria 3052</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lappas, Martha" sort="Lappas, Martha" uniqKey="Lappas M" first="Martha" last="Lappas">Martha Lappas</name>
<affiliation wicri:level="4"><nlm:affiliation>Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria 3084</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loudovaris, Thomas" sort="Loudovaris, Thomas" uniqKey="Loudovaris T" first="Thomas" last="Loudovaris">Thomas Loudovaris</name>
<affiliation wicri:level="1"><nlm:affiliation>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065</wicri:regionArea>
<wicri:noRegion>Victoria 3065</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mannering, Stuart I" sort="Mannering, Stuart I" uniqKey="Mannering S" first="Stuart I" last="Mannering">Stuart I. Mannering</name>
<affiliation wicri:level="1"><nlm:affiliation>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065</wicri:regionArea>
<wicri:noRegion>Victoria 3065</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Westall, Glen P" sort="Westall, Glen P" uniqKey="Westall G" first="Glen P" last="Westall">Glen P. Westall</name>
<affiliation wicri:level="1"><nlm:affiliation>Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria 3004</wicri:regionArea>
<wicri:noRegion>Victoria 3004</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Elliot, Michael" sort="Elliot, Michael" uniqKey="Elliot M" first="Michael" last="Elliot">Michael Elliot</name>
<affiliation wicri:level="4"><nlm:affiliation>Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Sydney Medical School, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea>
<orgName type="university">Université de Sydney</orgName>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050</wicri:regionArea>
<wicri:noRegion>New South Wales 2050</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G" last="Tangye">Stuart G. Tangye</name>
<affiliation wicri:level="1"><nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010</wicri:regionArea>
<wicri:noRegion>New South Wales 2010</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
<wicri:noRegion>New South Wales 2052</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wakim, Linda M" sort="Wakim, Linda M" uniqKey="Wakim L" first="Linda M" last="Wakim">Linda M. Wakim</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004</wicri:regionArea>
<wicri:noRegion>Victoria 3004</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nguyen, Thi H O" sort="Nguyen, Thi H O" uniqKey="Nguyen T" first="Thi H O" last="Nguyen">Thi H O. Nguyen</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Science translational medicine</title>
<idno type="eISSN">1946-6242</idno>
<imprint><date when="2018" type="published">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Antibody-Producing Cells (metabolism)</term>
<term>Antigens, CD (metabolism)</term>
<term>B-Lymphocytes (immunology)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (metabolism)</term>
<term>Humans (MeSH)</term>
<term>Immunity, Cellular (MeSH)</term>
<term>Immunologic Memory (MeSH)</term>
<term>Influenza, Human (blood)</term>
<term>Influenza, Human (immunology)</term>
<term>T-Lymphocytes, Helper-Inducer (immunology)</term>
<term>Vaccination (MeSH)</term>
<term>Vaccines, Inactivated (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Antigènes CD (métabolisme)</term>
<term>Cellules productrices d'anticorps (métabolisme)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (métabolisme)</term>
<term>Grippe humaine (immunologie)</term>
<term>Grippe humaine (sang)</term>
<term>Humains (MeSH)</term>
<term>Immunité cellulaire (MeSH)</term>
<term>Lymphocytes B (immunologie)</term>
<term>Lymphocytes T auxiliaires (immunologie)</term>
<term>Mémoire immunologique (MeSH)</term>
<term>Vaccination (MeSH)</term>
<term>Vaccins inactivés (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term>
<term>Vaccines, Inactivated</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Influenza, Human</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Grippe humaine</term>
<term>Lymphocytes B</term>
<term>Lymphocytes T auxiliaires</term>
<term>Vaccins inactivés</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>B-Lymphocytes</term>
<term>Influenza, Human</term>
<term>T-Lymphocytes, Helper-Inducer</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Antibody-Producing Cells</term>
<term>Antigens, CD</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes CD</term>
<term>Cellules productrices d'anticorps</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Grippe humaine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Humans</term>
<term>Immunity, Cellular</term>
<term>Immunologic Memory</term>
<term>Vaccination</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Humains</term>
<term>Immunité cellulaire</term>
<term>Mémoire immunologique</term>
<term>Vaccination</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T<sub>FH</sub>
) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5<sup>-</sup>
CXCR3<sup>+</sup>
antibody-secreting B cell population, CD21<sup>hi</sup>
CD27<sup>+</sup>
memory B cells, and CD21<sup>lo</sup>
CD27<sup>+</sup>
B cells. Activation of circulating T<sub>FH</sub>
cells correlated with the development of both CD21<sup>lo</sup>
and CD21<sup>hi</sup>
memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8<sup>+</sup>
, mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21<sup>hi</sup>
CD27<sup>+</sup>
) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating T<sub>FH</sub>
cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29444980</PMID>
<DateCompleted><Year>2019</Year>
<Month>09</Month>
<Day>16</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>09</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1946-6242</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>10</Volume>
<Issue>428</Issue>
<PubDate><Year>2018</Year>
<Month>02</Month>
<Day>14</Day>
</PubDate>
</JournalIssue>
<Title>Science translational medicine</Title>
<ISOAbbreviation>Sci Transl Med</ISOAbbreviation>
</Journal>
<ArticleTitle>Circulating T<sub>FH</sub>
cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">eaan8405</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/scitranslmed.aan8405</ELocationID>
<Abstract><AbstractText>Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T<sub>FH</sub>
) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5<sup>-</sup>
CXCR3<sup>+</sup>
antibody-secreting B cell population, CD21<sup>hi</sup>
CD27<sup>+</sup>
memory B cells, and CD21<sup>lo</sup>
CD27<sup>+</sup>
B cells. Activation of circulating T<sub>FH</sub>
cells correlated with the development of both CD21<sup>lo</sup>
and CD21<sup>hi</sup>
memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8<sup>+</sup>
, mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21<sup>hi</sup>
CD27<sup>+</sup>
) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating T<sub>FH</sub>
cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.</AbstractText>
<CopyrightInformation>Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Koutsakos</LastName>
<ForeName>Marios</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0001-9994-9723</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wheatley</LastName>
<ForeName>Adam K</ForeName>
<Initials>AK</Initials>
<Identifier Source="ORCID">0000-0002-5593-9387</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Loh</LastName>
<ForeName>Liyen</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Clemens</LastName>
<ForeName>E Bridie</ForeName>
<Initials>EB</Initials>
<Identifier Source="ORCID">0000-0002-8473-4743</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sant</LastName>
<ForeName>Sneha</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nüssing</LastName>
<ForeName>Simone</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">0000-0002-0685-3413</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fox</LastName>
<ForeName>Annette</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">0000-0002-0565-7146</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chung</LastName>
<ForeName>Amy W</ForeName>
<Initials>AW</Initials>
<Identifier Source="ORCID">0000-0003-0020-9704</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Laurie</LastName>
<ForeName>Karen L</ForeName>
<Initials>KL</Initials>
<AffiliationInfo><Affiliation>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hurt</LastName>
<ForeName>Aeron C</ForeName>
<Initials>AC</Initials>
<AffiliationInfo><Affiliation>World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Rockman</LastName>
<ForeName>Steve</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Seqirus, 63 Poplar Road, Parkville, Victoria 3052, Australia.</Affiliation>
</AffiliationInfo>
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<ForeName>Martha</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Loudovaris</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0002-7038-2302</Identifier>
<AffiliationInfo><Affiliation>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mannering</LastName>
<ForeName>Stuart I</ForeName>
<Initials>SI</Initials>
<Identifier Source="ORCID">0000-0003-3497-3559</Identifier>
<AffiliationInfo><Affiliation>Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Westall</LastName>
<ForeName>Glen P</ForeName>
<Initials>GP</Initials>
<AffiliationInfo><Affiliation>Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Elliot</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0001-5654-2114</Identifier>
<AffiliationInfo><Affiliation>Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tangye</LastName>
<ForeName>Stuart G</ForeName>
<Initials>SG</Initials>
<Identifier Source="ORCID">0000-0002-5360-5180</Identifier>
<AffiliationInfo><Affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wakim</LastName>
<ForeName>Linda M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kent</LastName>
<ForeName>Stephen J</ForeName>
<Initials>SJ</Initials>
<Identifier Source="ORCID">0000-0002-8539-4891</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nguyen</LastName>
<ForeName>Thi H O</ForeName>
<Initials>THO</Initials>
<Identifier Source="ORCID">0000-0002-9294-7693</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kedzierska</LastName>
<ForeName>Katherine</ForeName>
<Initials>K</Initials>
<Identifier Source="ORCID">0000-0001-6141-335X</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.</Affiliation>
</AffiliationInfo>
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</AuthorList>
<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Sci Transl Med</MedlineTA>
<NlmUniqueID>101505086</NlmUniqueID>
<ISSNLinking>1946-6234</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015164">Vaccines, Inactivated</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D000921" MajorTopicYN="N">Antibody-Producing Cells</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019267" MajorTopicYN="N">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007111" MajorTopicYN="Y">Immunity, Cellular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007156" MajorTopicYN="Y">Immunologic Memory</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006377" MajorTopicYN="N">T-Lymphocytes, Helper-Inducer</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014611" MajorTopicYN="N">Vaccination</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015164" MajorTopicYN="N">Vaccines, Inactivated</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
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<Month>05</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2017</Year>
<Month>09</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>12</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2018</Year>
<Month>2</Month>
<Day>16</Day>
<Hour>6</Hour>
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<PubMedPubDate PubStatus="pubmed"><Year>2018</Year>
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<Hour>6</Hour>
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<PubMedPubDate PubStatus="medline"><Year>2019</Year>
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<Day>17</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<affiliations><list><country><li>Australie</li>
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<region><li>Nouvelle-Galles du Sud</li>
<li>Victoria (État)</li>
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<settlement><li>Melbourne</li>
<li>Sydney</li>
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<orgName><li>Université de Melbourne</li>
<li>Université de Sydney</li>
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<name sortKey="Chung, Amy W" sort="Chung, Amy W" uniqKey="Chung A" first="Amy W" last="Chung">Amy W. Chung</name>
<name sortKey="Clemens, E Bridie" sort="Clemens, E Bridie" uniqKey="Clemens E" first="E Bridie" last="Clemens">E Bridie Clemens</name>
<name sortKey="Elliot, Michael" sort="Elliot, Michael" uniqKey="Elliot M" first="Michael" last="Elliot">Michael Elliot</name>
<name sortKey="Elliot, Michael" sort="Elliot, Michael" uniqKey="Elliot M" first="Michael" last="Elliot">Michael Elliot</name>
<name sortKey="Fox, Annette" sort="Fox, Annette" uniqKey="Fox A" first="Annette" last="Fox">Annette Fox</name>
<name sortKey="Hurt, Aeron C" sort="Hurt, Aeron C" uniqKey="Hurt A" first="Aeron C" last="Hurt">Aeron C. Hurt</name>
<name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<name sortKey="Lappas, Martha" sort="Lappas, Martha" uniqKey="Lappas M" first="Martha" last="Lappas">Martha Lappas</name>
<name sortKey="Laurie, Karen L" sort="Laurie, Karen L" uniqKey="Laurie K" first="Karen L" last="Laurie">Karen L. Laurie</name>
<name sortKey="Loh, Liyen" sort="Loh, Liyen" uniqKey="Loh L" first="Liyen" last="Loh">Liyen Loh</name>
<name sortKey="Loudovaris, Thomas" sort="Loudovaris, Thomas" uniqKey="Loudovaris T" first="Thomas" last="Loudovaris">Thomas Loudovaris</name>
<name sortKey="Mannering, Stuart I" sort="Mannering, Stuart I" uniqKey="Mannering S" first="Stuart I" last="Mannering">Stuart I. Mannering</name>
<name sortKey="Nguyen, Thi H O" sort="Nguyen, Thi H O" uniqKey="Nguyen T" first="Thi H O" last="Nguyen">Thi H O. Nguyen</name>
<name sortKey="Nussing, Simone" sort="Nussing, Simone" uniqKey="Nussing S" first="Simone" last="Nüssing">Simone Nüssing</name>
<name sortKey="Rockman, Steve" sort="Rockman, Steve" uniqKey="Rockman S" first="Steve" last="Rockman">Steve Rockman</name>
<name sortKey="Rockman, Steve" sort="Rockman, Steve" uniqKey="Rockman S" first="Steve" last="Rockman">Steve Rockman</name>
<name sortKey="Sant, Sneha" sort="Sant, Sneha" uniqKey="Sant S" first="Sneha" last="Sant">Sneha Sant</name>
<name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G" last="Tangye">Stuart G. Tangye</name>
<name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G" last="Tangye">Stuart G. Tangye</name>
<name sortKey="Wakim, Linda M" sort="Wakim, Linda M" uniqKey="Wakim L" first="Linda M" last="Wakim">Linda M. Wakim</name>
<name sortKey="Westall, Glen P" sort="Westall, Glen P" uniqKey="Westall G" first="Glen P" last="Westall">Glen P. Westall</name>
<name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K" last="Wheatley">Adam K. Wheatley</name>
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