Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life.

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
31 Jan 2023
Historique:
pubmed: 14 2 2023
medline: 14 2 2023
entrez: 13 2 2023
Statut: epublish

Résumé

The dynamics of innate and adaptive immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to SARS-CoV-2 infection in infants and young children in the first weeks and months of life by analyzing blood samples collected before, during, and after infection with Omicron and Non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, were stably maintained for >300 days. Antigen-specific memory B cell (MCB) responses were durable for 150 days but waned thereafter. Somatic hypermutation of V-genes in MCB accumulated progressively over 9 months. The innate response was characterized by upregulation of activation markers on blood innate cells, and a plasma cytokine profile distinct from that seen in adults, with no inflammatory cytokines, but an early and transient accumulation of chemokines (CXCL10, IL8, IL-18R1, CSF-1, CX3CL1), and type I IFN. The latter was strongly correlated with viral load, and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell transcriptomics. Consistent with this, single-cell ATAC-seq revealed enhanced accessibility of chromatic loci targeted by interferon regulatory factors (IRFs) and reduced accessibility of AP-1 targeted loci, as well as traces of epigenetic imprinting in monocytes, during convalescence. Together, these data provide the first snapshot of immunity to infection during the initial weeks and months of life.

Identifiants

DOI: 10.1101/2023.01.28.23285133 PMID: 36778389 PMC: PMC9915811
pubmed: 36778389
doi: 10.1101/2023.01.28.23285133
pmc: PMC9915811
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : U19 AI167903
Pays : United States

Déclaration de conflit d'intérêts

Declaration of Interest Alessandro Sette is a consultant for Gritstone Bio, Flow Pharma, Moderna, AstraZeneca, Qiagen, Fortress, Gilead, Sanofi, Merck, RiverVest, MedaCorp, Turnstone, NA Vaccine Institute, Emervax, Gerson Lehrman Group and Guggenheim. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.

Auteurs

Florian Wimmers (F)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Molecular Medicine, Interfaculty Institute for Biochemistry, University of Tuebingen, Tuebingen, Germany.
DFG Cluster of Excellence 2180 'Image-guided and Functional Instructed Tumor Therapy' (iFIT), University of Tuebingen, Tuebingen, Germany.
German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Allison R Burrell (AR)

Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Environmental and Public Health Sciences, Division of Epidemiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Yupeng Feng (Y)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.

Hong Zheng (H)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.

Prabhu S Arunachalam (PS)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.

Mengyun Hu (M)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.

Sara Spranger (S)

Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Lindsay Nyhoff (L)

Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine.

Devyani Joshi (D)

Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine.

Meera Trisal (M)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.

Mayanka Awasthi (M)

Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA.

Lorenza Bellusci (L)

Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA.

Usama Ashraf (U)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.

Sangeeta Kowli (S)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Katherine C Konvinse (KC)

Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Emily Yang (E)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.

Michael Blanco (M)

Stanford Genomics Service Center, Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

Kathryn Pellegrini (K)

Yerkes National Primate Research Center, Atlanta, GA, USA.

Gregory Tharp (G)

Yerkes National Primate Research Center, Atlanta, GA, USA.

Thomas Hagan (T)

Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

R Sharon Chinthrajah (RS)

Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94305, USA.

Alba Grifoni (A)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.

Alessandro Sette (A)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.

Kari C Nadeau (KC)

Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94305, USA.

David B Haslam (DB)

Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Steven E Bosinger (SE)

Yerkes National Primate Research Center, Atlanta, GA, USA.
Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.

Jens Wrammert (J)

Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine.

Holden T Maecker (HT)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Paul J Utz (PJ)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.

Taia T Wang (TT)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Surender Khurana (S)

Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA.

Purvesh Khatri (P)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.

Mary A Staat (MA)

Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Bali Pulendran (B)

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Classifications MeSH