SARS-CoV-2 variants of concern elicit divergent early immune responses in hACE2 transgenic mice.
K18-hACE2
SARS-CoV-2
compartmentalization
immune response
variant of concern
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
23 Aug 2023
23 Aug 2023
Historique:
revised:
20
07
2023
received:
13
12
2022
accepted:
21
08
2023
pubmed:
23
8
2023
medline:
23
8
2023
entrez:
23
8
2023
Statut:
aheadofprint
Résumé
Knowledge about early immunity to SARS-CoV-2 variants of concern mainly comes from the analysis of human blood. Such data provide limited information about host responses at the site of infection and largely miss the initial events. To gain insights into compartmentalization and the early dynamics of host responses to different SARS-CoV-2 variants, we utilized human angiotensin converting enzyme 2 (hACE2) transgenic mice and tracked immune changes during the first days after infection by RNAseq, multiplex assays, and flow cytometry. Viral challenge infection led to divergent viral loads in the lungs, distinct inflammatory patterns, and innate immune cell accumulation in response to ancestral SARS-CoV-2, Beta (B.1.351) and Delta (B.1.617.2) variant of concern (VOC). Compared to other SARS-CoV-2 variants, infection with Beta (B.1.351) VOC spread promptly to the lungs, leading to increased inflammatory responses. SARS-CoV-2-specific antibodies and T cells developed within the first 7 days postinfection and were required to reduce viral spread and replication. Our studies show that VOCs differentially trigger transcriptional profiles and inflammation. This information contributes to the basic understanding of immune responses immediately postexposure to SARS-CoV-2 and is relevant for developing pan-VOC interventions including prophylactic vaccines.
Identifiants
pubmed: 37609807
doi: 10.1002/eji.202250332
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2250332Subventions
Organisme : BMBF
ID : 01KI20703
Organisme : CureVac SE
Organisme : GSK
Informations de copyright
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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