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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\u2010CoV\u20102 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\u2010CoV\u20102, Beta (B.1.351) and Delta (B.1.617.2) variant of concern (VOC). Compared to other SARS\u2010CoV\u20102 variants, infection with Beta (B.1.351) VOC spread promptly to the lungs, leading to increased inflammatory responses. SARS\u2010CoV\u20102\u2010specific 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\u2010CoV\u20102 and is relevant for developing pan\u2010VOC interventions including prophylactic vaccines.<\/jats:p>","DOI":"10.1002\/eji.202250332","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T08:35:26Z","timestamp":1692779726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SARS\u2010CoV\u20102 variants of concern elicit divergent early immune responses in hACE2 transgenic mice"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7493-6627","authenticated-orcid":false,"given":"Charlie","family":"Fricke","sequence":"first","affiliation":[{"name":"Institute of Immunology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Pfaff","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-806X","authenticated-orcid":false,"given":"Lorenz","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico Joel","family":"Halwe","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Timm","sequence":"additional","affiliation":[{"name":"Institute of Immunology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weda","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Immunology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Rauch","sequence":"additional","affiliation":[{"name":"CureVac SE  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Petsch","sequence":"additional","affiliation":[{"name":"CureVac SE  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donata","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Beer","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Corleis","sequence":"additional","affiliation":[{"name":"Institute of Immunology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca","family":"Dorhoi","sequence":"additional","affiliation":[{"name":"Institute of Immunology Friedrich\u2010Loeffler\u2010Institut  Greifswald\u2010Insel Riems Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2020.1778470"},{"key":"e_1_2_10_3_1","unstructured":"WHO.Tracking SARS\u2010CoV\u20102 variants; 2023 [cited 2023 Jun 26]. 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