SARS‐CoV‐2 variants of concern elicit divergent early immune responses in hACE2 transgenic mice

Abstract: 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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
SARS‐CoV‐2 variants of concern elicit divergent early immune responses in hACE2 transgenic mice ; day:07 ; month:09 ; year:2023 ; extent:18
European journal of immunology ; (07.09.2023) (gesamt 18)

Creator
Fricke, Charlie
Pfaff, Florian
Ulrich, Lorenz
Halwe, Nico Joel
Schön, Jacob
Timm, Laura
Hoffmann, Weda
Rauch, Susanne
Petsch, Benjamin
Hoffmann, Donata
Beer, Martin
Corleis, Björn
Dorhoi, Anca

DOI
10.1002/eji.202250332
URN
urn:nbn:de:101:1-2023090815075035270498
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:59 AM CEST

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