Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination.
| Title: | Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. |
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| Authors: | Röltgen K; Department of Pathology, Stanford University, Stanford, CA, USA.; Nielsen SCA; Department of Pathology, Stanford University, Stanford, CA, USA.; Silva O; Department of Pathology, Stanford University, Stanford, CA, USA.; Younes SF; Department of Pathology, Stanford University, Stanford, CA, USA.; Zaslavsky M; Department of Pathology, Stanford University, Stanford, CA, USA.; Costales C; Department of Pathology, Stanford University, Stanford, CA, USA.; Yang F; Department of Pathology, Stanford University, Stanford, CA, USA.; Wirz OF; Department of Pathology, Stanford University, Stanford, CA, USA.; Solis D; Department of Pathology, Stanford University, Stanford, CA, USA.; Hoh RA; Department of Pathology, Stanford University, Stanford, CA, USA.; Wang A; Department of Pathology, Stanford University, Stanford, CA, USA.; Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.; Colburg D; Department of Pathology, Stanford University, Stanford, CA, USA.; Zhao S; Department of Pathology, Stanford University, Stanford, CA, USA.; Haraguchi E; Department of Pathology, Stanford University, Stanford, CA, USA.; Lee AS; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Shah MM; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Manohar M; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Chang I; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Gao F; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.; Mallajosyula V; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.; Li C; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.; Liu J; Stanford Health Library, Stanford, CA, USA.; Shoura MJ; Department of Pathology, Stanford University, Stanford, CA, USA.; Sindher SB; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Parsons E; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.; Dashdorj NJ; Onom Foundation, Ulaanbaatar 17013, Mongolia; Liver Center, Ulaanbaatar 14230, Mongolia.; Dashdorj ND; Onom Foundation, Ulaanbaatar 17013, Mongolia.; Monroe R; Advanced Cell Diagnostics, Newark, CA, USA.; Serrano GE; Banner Sun Health Research Institute, Sun City, AZ, USA.; Beach TG; Banner Sun Health Research Institute, Sun City, AZ, USA.; Chinthrajah RS; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, USA.; Charville GW; Department of Pathology, Stanford University, Stanford, CA, USA.; Wilbur JL; Meso Scale Diagnostics LLC, Rockville, MD, USA.; Wohlstadter JN; Meso Scale Diagnostics LLC, Rockville, MD, USA.; Davis MM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.; Pulendran B; Department of Pathology, Stanford University, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.; Troxell ML; Department of Pathology, Stanford University, Stanford, CA, USA.; Sigal GB; Meso Scale Diagnostics LLC, Rockville, MD, USA.; Natkunam Y; Department of Pathology, Stanford University, Stanford, CA, USA.; Pinsky BA; Department of Pathology, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.; Nadeau KC; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, USA.; Boyd SD; Department of Pathology, Stanford University, Stanford, CA, USA; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA. Electronic address: publications_scott_boyd@stanford.edu. |
| Source: | Cell [Cell] 2022 Mar 17; Vol. 185 (6), pp. 1025-1040.e14. Date of Electronic Publication: 2022 Jan 25. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, Ma : Cell Press; Original Publication: Cambridge, MIT Press. |
| MeSH Terms: | COVID-19*/prevention & control ; Antibodies, Viral* ; BNT162 Vaccine* ; Germinal Center*; SARS-CoV-2/genetics ; Antigens, Viral ; Humans ; Spike Glycoprotein, Coronavirus ; Vaccination |
| Abstract: | During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.; (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests S.D.B. has consulted for Regeneron, Sanofi, Novartis, and Janssen on topics unrelated to this study and owns stock in AbCellera Biologics. K.C.N. reports grants from the National Institute of Allergy and Infectious Diseases (NIAID), Food Allergy Research & Education (FARE), End Allergies Together (EAT), National Heart Lung and Blood Institute (NHLBI), and National Institute of Environmental Health Sciences (NIEHS). K.C.N. is Director of FARE and World Allergy Organization (WAO) Center of Excellence at Stanford; Adviser at Cour Pharmaceuticals; Cofounder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member for the Immune Tolerance Network (ITN) of NIAID; recipient of a Research Sponsorship from Nestle; Consultant and Advisory Board Member at Before Brands, Alladapt, IgGenix, NHLBI, and ProBio; and Data and Safety Monitoring Board member at NHLBI. J.L.W., J.N.W., and G.B.S. are employees of Meso Scale Diagnostics (MSD). |
| Comments: | Comment in: Trends Immunol. 2022 Apr;43(4):271-273. doi: 10.1016/j.it.2022.02.009.. (PMID: 35272935) |
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| Grant Information: | U54 CA260517 United States CA NCI NIH HHS; U19 AI057229 United States AI NIAID NIH HHS; P30 AG072980 United States AG NIA NIH HHS; R01 AI127877 United States AI NIAID NIH HHS; P01 AI153559 United States AI NIAID NIH HHS; P30 AG019610 United States AG NIA NIH HHS; R01 AI130398 United States AI NIAID NIH HHS; HHSN272201700013C United States AI NIAID NIH HHS; U19 AI167903 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: Astra Zeneca; BBIBP-CorV; BNT162b2; BioNTech-Pfizer; COVID-19; ChAdOx1-S; Delta variant; Gam-COVID-Vac; Moderna; SARS-CoV-2; SARS-CoV-2 variants of concern; Sinopharm; Sputnik V; antibodies; autopsy; endemic coronaviruses; imprinting; lymph node germinal center; mRNA-1273; vaccine |
| Substance Nomenclature: | 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (BNT162 Vaccine); 0 (Spike Glycoprotein, Coronavirus); 0 (spike protein, SARS-CoV-2) |
| SCR Organism: | SARS-CoV-2 variants |
| Entry Date(s): | Date Created: 20220212 Date Completed: 20220415 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8786601 |
| DOI: | 10.1016/j.cell.2022.01.018 |
| PMID: | 35148837 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't