Modeling human adaptive immune responses with tonsil organoids.
Identifieur interne : 000060 ( Main/Exploration ); précédent : 000059; suivant : 000061Modeling human adaptive immune responses with tonsil organoids.
Auteurs : Lisa E. Wagar [États-Unis] ; Ameen Salahudeen [États-Unis] ; Christian M. Constantz [États-Unis] ; Ben S. Wendel [États-Unis] ; Michael M. Lyons [États-Unis] ; Vamsee Mallajosyula [États-Unis] ; Lauren P. Jatt [États-Unis] ; Julia Z. Adamska [États-Unis] ; Lisa K. Blum [États-Unis] ; Neha Gupta [États-Unis] ; Katherine J L. Jackson [États-Unis] ; Fan Yang [États-Unis] ; Katharina Röltgen [États-Unis] ; Krishna M. Roskin [États-Unis] ; Kelly M. Blaine [États-Unis] ; Kara D. Meister [États-Unis] ; Iram N. Ahmad [États-Unis] ; Mario Cortese [États-Unis] ; Emery G. Dora [États-Unis] ; Sean N. Tucker [États-Unis] ; Anne I. Sperling [États-Unis] ; Aarti Jain [États-Unis] ; D Huw Davies [États-Unis] ; Philip L. Felgner [États-Unis] ; Gregory B. Hammer [États-Unis] ; Peter S. Kim [États-Unis] ; William H. Robinson [États-Unis] ; Scott D. Boyd [États-Unis] ; Calvin J. Kuo [États-Unis] ; Mark M. Davis [États-Unis]Source :
- Nature medicine [ 1546-170X ] ; 2021.
Descripteurs français
- KwdFr :
- Adjuvants immunologiques (MeSH), Centre germinatif (cytologie), Glycoprotéine hémagglutinine du virus influenza (MeSH), Humains (MeSH), Lymphocytes B (cytologie), Lymphocytes B (immunologie), Lymphocytes T (immunologie), Organoïdes (cytologie), Organoïdes (immunologie), Techniques in vitro (MeSH), Tissu lymphoïde (immunologie), Tonsille palatine (immunologie), Vaccin contre la rougeole, les oreillons et la rubéole (immunologie), Vaccins antigrippaux (immunologie), Vaccins antirabiques (immunologie).
- MESH :
- cytologie : Centre germinatif, Lymphocytes B, Organoïdes.
- immunologie : Lymphocytes B, Lymphocytes T, Organoïdes, Tissu lymphoïde, Tonsille palatine, Vaccin contre la rougeole, les oreillons et la rubéole, Vaccins antigrippaux, Vaccins antirabiques.
- Adjuvants immunologiques, Glycoprotéine hémagglutinine du virus influenza, Humains, Techniques in vitro.
English descriptors
- KwdEn :
- Adjuvants, Immunologic (MeSH), B-Lymphocytes (cytology), B-Lymphocytes (immunology), COVID-19 Vaccines (immunology), Germinal Center (cytology), Hemagglutinin Glycoproteins, Influenza Virus (MeSH), Humans (MeSH), In Vitro Techniques (MeSH), Influenza Vaccines (immunology), Lymphoid Tissue (immunology), Measles-Mumps-Rubella Vaccine (immunology), Organoids (cytology), Organoids (immunology), Palatine Tonsil (immunology), Rabies Vaccines (immunology), T-Lymphocytes (immunology).
- MESH :
- chemical , immunology : COVID-19 Vaccines, Influenza Vaccines, Measles-Mumps-Rubella Vaccine, Rabies Vaccines.
- chemical : Adjuvants, Immunologic, Hemagglutinin Glycoproteins, Influenza Virus.
- cytology : B-Lymphocytes, Germinal Center, Organoids.
- immunology : B-Lymphocytes, Lymphoid Tissue, Organoids, Palatine Tonsil, T-Lymphocytes.
- Humans, In Vitro Techniques.
Abstract
Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
DOI: 10.1038/s41591-020-01145-0
PubMed: 33432170
Affiliations:
- États-Unis
- Californie, Illinois
- Chicago, Stanford (Californie)
- Université Stanford, Université de Chicago, Université de l'Illinois à Chicago
Links toward previous steps (curation, corpus...)
Le document en format XML
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Blaine</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Meister, Kara D" sort="Meister, Kara D" uniqKey="Meister K" first="Kara D" last="Meister">Kara D. Meister</name><affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ahmad, Iram N" sort="Ahmad, Iram N" uniqKey="Ahmad I" first="Iram N" last="Ahmad">Iram N. Ahmad</name><affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Cortese, Mario" sort="Cortese, Mario" uniqKey="Cortese M" first="Mario" last="Cortese">Mario Cortese</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Dora, Emery G" sort="Dora, Emery G" uniqKey="Dora E" first="Emery G" last="Dora">Emery G. Dora</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Tucker, Sean N" sort="Tucker, Sean N" uniqKey="Tucker S" first="Sean N" last="Tucker">Sean N. Tucker</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Sperling, Anne I" sort="Sperling, Anne I" uniqKey="Sperling A" first="Anne I" last="Sperling">Anne I. Sperling</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Jain, Aarti" sort="Jain, Aarti" uniqKey="Jain A" first="Aarti" last="Jain">Aarti Jain</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Davies, D Huw" sort="Davies, D Huw" uniqKey="Davies D" first="D Huw" last="Davies">D Huw Davies</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Felgner, Philip L" sort="Felgner, Philip L" uniqKey="Felgner P" first="Philip L" last="Felgner">Philip L. Felgner</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Hammer, Gregory B" sort="Hammer, Gregory B" uniqKey="Hammer G" first="Gregory B" last="Hammer">Gregory B. Hammer</name><affiliation wicri:level="2"><nlm:affiliation>Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kim, Peter S" sort="Kim, Peter S" uniqKey="Kim P" first="Peter S" last="Kim">Peter S. Kim</name><affiliation wicri:level="4"><nlm:affiliation>Stanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Stanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Robinson, William H" sort="Robinson, William H" uniqKey="Robinson W" first="William H" last="Robinson">William H. Robinson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Boyd, Scott D" sort="Boyd, Scott D" uniqKey="Boyd S" first="Scott D" last="Boyd">Scott D. Boyd</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kuo, Calvin J" sort="Kuo, Calvin J" uniqKey="Kuo C" first="Calvin J" last="Kuo">Calvin J. Kuo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Davis, Mark M" sort="Davis, Mark M" uniqKey="Davis M" first="Mark M" last="Davis">Mark M. Davis</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33432170</idno><idno type="pmid">33432170</idno><idno type="doi">10.1038/s41591-020-01145-0</idno><idno type="wicri:Area/Main/Corpus">000049</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000049</idno><idno type="wicri:Area/Main/Curation">000049</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000049</idno><idno type="wicri:Area/Main/Exploration">000049</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Modeling human adaptive immune responses with tonsil organoids.</title><author><name sortKey="Wagar, Lisa E" sort="Wagar, Lisa E" uniqKey="Wagar L" first="Lisa E" last="Wagar">Lisa E. Wagar</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Salahudeen, Ameen" sort="Salahudeen, Ameen" uniqKey="Salahudeen A" first="Ameen" last="Salahudeen">Ameen Salahudeen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Constantz, Christian M" sort="Constantz, Christian M" uniqKey="Constantz C" first="Christian M" last="Constantz">Christian M. Constantz</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Wendel, Ben S" sort="Wendel, Ben S" uniqKey="Wendel B" first="Ben S" last="Wendel">Ben S. Wendel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Lyons, Michael M" sort="Lyons, Michael M" uniqKey="Lyons M" first="Michael M" last="Lyons">Michael M. Lyons</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Mallajosyula, Vamsee" sort="Mallajosyula, Vamsee" uniqKey="Mallajosyula V" first="Vamsee" last="Mallajosyula">Vamsee Mallajosyula</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Jatt, Lauren P" sort="Jatt, Lauren P" uniqKey="Jatt L" first="Lauren P" last="Jatt">Lauren P. Jatt</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Adamska, Julia Z" sort="Adamska, Julia Z" uniqKey="Adamska J" first="Julia Z" last="Adamska">Julia Z. Adamska</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Blum, Lisa K" sort="Blum, Lisa K" uniqKey="Blum L" first="Lisa K" last="Blum">Lisa K. Blum</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Gupta, Neha" sort="Gupta, Neha" uniqKey="Gupta N" first="Neha" last="Gupta">Neha Gupta</name><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Jackson, Katherine J L" sort="Jackson, Katherine J L" uniqKey="Jackson K" first="Katherine J L" last="Jackson">Katherine J L. Jackson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Yang, Fan" sort="Yang, Fan" uniqKey="Yang F" first="Fan" last="Yang">Fan Yang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Roltgen, Katharina" sort="Roltgen, Katharina" uniqKey="Roltgen K" first="Katharina" last="Röltgen">Katharina Röltgen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Roskin, Krishna M" sort="Roskin, Krishna M" uniqKey="Roskin K" first="Krishna M" last="Roskin">Krishna M. Roskin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Blaine, Kelly M" sort="Blaine, Kelly M" uniqKey="Blaine K" first="Kelly M" last="Blaine">Kelly M. Blaine</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Meister, Kara D" sort="Meister, Kara D" uniqKey="Meister K" first="Kara D" last="Meister">Kara D. Meister</name><affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ahmad, Iram N" sort="Ahmad, Iram N" uniqKey="Ahmad I" first="Iram N" last="Ahmad">Iram N. Ahmad</name><affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Cortese, Mario" sort="Cortese, Mario" uniqKey="Cortese M" first="Mario" last="Cortese">Mario Cortese</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Dora, Emery G" sort="Dora, Emery G" uniqKey="Dora E" first="Emery G" last="Dora">Emery G. Dora</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Tucker, Sean N" sort="Tucker, Sean N" uniqKey="Tucker S" first="Sean N" last="Tucker">Sean N. Tucker</name><affiliation wicri:level="2"><nlm:affiliation>Vaxart, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaxart, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Sperling, Anne I" sort="Sperling, Anne I" uniqKey="Sperling A" first="Anne I" last="Sperling">Anne I. Sperling</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Jain, Aarti" sort="Jain, Aarti" uniqKey="Jain A" first="Aarti" last="Jain">Aarti Jain</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Davies, D Huw" sort="Davies, D Huw" uniqKey="Davies D" first="D Huw" last="Davies">D Huw Davies</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Felgner, Philip L" sort="Felgner, Philip L" uniqKey="Felgner P" first="Philip L" last="Felgner">Philip L. Felgner</name><affiliation wicri:level="2"><nlm:affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Hammer, Gregory B" sort="Hammer, Gregory B" uniqKey="Hammer G" first="Gregory B" last="Hammer">Gregory B. Hammer</name><affiliation wicri:level="2"><nlm:affiliation>Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kim, Peter S" sort="Kim, Peter S" uniqKey="Kim P" first="Peter S" last="Kim">Peter S. Kim</name><affiliation wicri:level="4"><nlm:affiliation>Stanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Stanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author><author><name sortKey="Robinson, William H" sort="Robinson, William H" uniqKey="Robinson W" first="William H" last="Robinson">William H. Robinson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Boyd, Scott D" sort="Boyd, Scott D" uniqKey="Boyd S" first="Scott D" last="Boyd">Scott D. Boyd</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kuo, Calvin J" sort="Kuo, Calvin J" uniqKey="Kuo C" first="Calvin J" last="Kuo">Calvin J. Kuo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Davis, Mark M" sort="Davis, Mark M" uniqKey="Davis M" first="Mark M" last="Davis">Mark M. Davis</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, Stanford University, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Stanford (Californie)</settlement></placeName><orgName type="university">Université Stanford</orgName></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="eISSN">1546-170X</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adjuvants, Immunologic (MeSH)</term><term>B-Lymphocytes (cytology)</term><term>B-Lymphocytes (immunology)</term><term>COVID-19 Vaccines (immunology)</term><term>Germinal Center (cytology)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (MeSH)</term><term>Humans (MeSH)</term><term>In Vitro Techniques (MeSH)</term><term>Influenza Vaccines (immunology)</term><term>Lymphoid Tissue (immunology)</term><term>Measles-Mumps-Rubella Vaccine (immunology)</term><term>Organoids (cytology)</term><term>Organoids (immunology)</term><term>Palatine Tonsil (immunology)</term><term>Rabies Vaccines (immunology)</term><term>T-Lymphocytes (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adjuvants immunologiques (MeSH)</term><term>Centre germinatif (cytologie)</term><term>Glycoprotéine hémagglutinine du virus influenza (MeSH)</term><term>Humains (MeSH)</term><term>Lymphocytes B (cytologie)</term><term>Lymphocytes B (immunologie)</term><term>Lymphocytes T (immunologie)</term><term>Organoïdes (cytologie)</term><term>Organoïdes (immunologie)</term><term>Techniques in vitro (MeSH)</term><term>Tissu lymphoïde (immunologie)</term><term>Tonsille palatine (immunologie)</term><term>Vaccin contre la rougeole, les oreillons et la rubéole (immunologie)</term><term>Vaccins antigrippaux (immunologie)</term><term>Vaccins antirabiques (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>COVID-19 Vaccines</term><term>Influenza Vaccines</term><term>Measles-Mumps-Rubella Vaccine</term><term>Rabies Vaccines</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Adjuvants, Immunologic</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Centre germinatif</term><term>Lymphocytes B</term><term>Organoïdes</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>B-Lymphocytes</term><term>Germinal Center</term><term>Organoids</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes B</term><term>Lymphocytes T</term><term>Organoïdes</term><term>Tissu lymphoïde</term><term>Tonsille palatine</term><term>Vaccin contre la rougeole, les oreillons et la rubéole</term><term>Vaccins antigrippaux</term><term>Vaccins antirabiques</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>B-Lymphocytes</term><term>Lymphoid Tissue</term><term>Organoids</term><term>Palatine Tonsil</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>In Vitro Techniques</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adjuvants immunologiques</term><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Humains</term><term>Techniques in vitro</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33432170</PMID><DateCompleted><Year>2021</Year><Month>01</Month><Day>22</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-170X</ISSN><JournalIssue CitedMedium="Internet"><Volume>27</Volume><Issue>1</Issue><PubDate><Year>2021</Year><Month>01</Month></PubDate></JournalIssue><Title>Nature medicine</Title><ISOAbbreviation>Nat Med</ISOAbbreviation></Journal><ArticleTitle>Modeling human adaptive immune responses with tonsil organoids.</ArticleTitle><Pagination><MedlinePgn>125-135</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41591-020-01145-0</ELocationID><Abstract><AbstractText>Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wagar</LastName><ForeName>Lisa E</ForeName><Initials>LE</Initials><Identifier Source="ORCID">0000-0001-5980-3586</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salahudeen</LastName><ForeName>Ameen</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Constantz</LastName><ForeName>Christian M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wendel</LastName><ForeName>Ben S</ForeName><Initials>BS</Initials><Identifier Source="ORCID">0000-0001-6896-3354</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lyons</LastName><ForeName>Michael M</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mallajosyula</LastName><ForeName>Vamsee</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jatt</LastName><ForeName>Lauren P</ForeName><Initials>LP</Initials><Identifier Source="ORCID">0000-0001-7034-9046</Identifier><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adamska</LastName><ForeName>Julia Z</ForeName><Initials>JZ</Initials><AffiliationInfo><Affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blum</LastName><ForeName>Lisa K</ForeName><Initials>LK</Initials><Identifier Source="ORCID">0000-0002-7921-8939</Identifier><AffiliationInfo><Affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gupta</LastName><ForeName>Neha</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jackson</LastName><ForeName>Katherine J L</ForeName><Initials>KJL</Initials><Identifier Source="ORCID">0000-0002-9952-7069</Identifier><AffiliationInfo><Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Fan</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0003-4821-6583</Identifier><AffiliationInfo><Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Röltgen</LastName><ForeName>Katharina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roskin</LastName><ForeName>Krishna M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blaine</LastName><ForeName>Kelly M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meister</LastName><ForeName>Kara D</ForeName><Initials>KD</Initials><AffiliationInfo><Affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ahmad</LastName><ForeName>Iram N</ForeName><Initials>IN</Initials><AffiliationInfo><Affiliation>Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cortese</LastName><ForeName>Mario</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Vaxart, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dora</LastName><ForeName>Emery G</ForeName><Initials>EG</Initials><AffiliationInfo><Affiliation>Vaxart, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tucker</LastName><ForeName>Sean N</ForeName><Initials>SN</Initials><AffiliationInfo><Affiliation>Vaxart, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sperling</LastName><ForeName>Anne I</ForeName><Initials>AI</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jain</LastName><ForeName>Aarti</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davies</LastName><ForeName>D Huw</ForeName><Initials>DH</Initials><AffiliationInfo><Affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Felgner</LastName><ForeName>Philip L</ForeName><Initials>PL</Initials><AffiliationInfo><Affiliation>Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hammer</LastName><ForeName>Gregory B</ForeName><Initials>GB</Initials><AffiliationInfo><Affiliation>Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Peter S</ForeName><Initials>PS</Initials><Identifier Source="ORCID">0000-0001-6503-4541</Identifier><AffiliationInfo><Affiliation>Stanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robinson</LastName><ForeName>William H</ForeName><Initials>WH</Initials><AffiliationInfo><Affiliation>Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyd</LastName><ForeName>Scott D</ForeName><Initials>SD</Initials><Identifier Source="ORCID">0000-0003-0963-044X</Identifier><AffiliationInfo><Affiliation>Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuo</LastName><ForeName>Calvin J</ForeName><Initials>CJ</Initials><Identifier Source="ORCID">0000-0002-7427-5985</Identifier><AffiliationInfo><Affiliation>Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davis</LastName><ForeName>Mark M</ForeName><Initials>MM</Initials><Identifier Source="ORCID">0000-0001-6868-657X</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>5U19AI05722915</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>1R01AI130398</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>U54CA224081</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>U19AI116484</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>U01CA217851</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>U01DK085527</GrantID><Agency>U.S. Department of Health & Human Services | National Institutes of Health (NIH)</Agency><Country>International</Country></Grant><Grant><GrantID>N/A</GrantID><Agency>Howard Hughes Medical Institute (HHMI)</Agency><Country>International</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Nat Med</MedlineTA><NlmUniqueID>9502015</NlmUniqueID><ISSNLinking>1078-8956</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000276">Adjuvants, Immunologic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000086663">COVID-19 Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C543345">H1N1 virus hemagglutinin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D022542">Measles-Mumps-Rubella Vaccine</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011819">Rabies Vaccines</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000276" MajorTopicYN="N">Adjuvants, Immunologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086663" MajorTopicYN="N">COVID-19 Vaccines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018858" MajorTopicYN="N">Germinal Center</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019267" MajorTopicYN="N">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D066298" MajorTopicYN="N">In Vitro Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008221" MajorTopicYN="N">Lymphoid Tissue</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D022542" MajorTopicYN="N">Measles-Mumps-Rubella Vaccine</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009940" MajorTopicYN="N">Organoids</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014066" MajorTopicYN="N">Palatine Tonsil</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011819" MajorTopicYN="N">Rabies Vaccines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>03</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>10</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>1</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>1</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>1</Month><Day>12</Day><Hour>6</Hour><Minute>8</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33432170</ArticleId><ArticleId IdType="doi">10.1038/s41591-020-01145-0</ArticleId><ArticleId IdType="pii">10.1038/s41591-020-01145-0</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Behring, E. 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