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Autor(en) / Beteiligte
Titel
Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19
Ist Teil von
  • Human vaccines & immunotherapeutics, 2022-11, Vol.18 (5), p.2048622-2048622
Ort / Verlag
United States: Taylor & Francis
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
  • We report a Human Immune System (HIS)-humanized mouse model ("DRAGA": HLA-A2.HLA-DR4.Rag1KO.IL-2 RγcKO.NOD) for COVID-19 research. DRAGA mice express transgenically HLA-class I and class-II molecules in the mouse thymus to promote human T cell development and human B cell Ig-class switching. When infused with human hematopoietic stem cells from cord blood reconstitute a functional human immune system, as well as human epi/endothelial cells in lung and upper respiratory airways expressing the human ACE2 receptor for SARS-CoV-2. The DRAGA mice were able to sustain SARS-CoV-2 infection for at least 25 days. Infected mice showed replicating virus in the lungs, deteriorating clinical condition, and human-like lung immunopathology including human lymphocyte infiltrates, microthrombi and pulmonary sequelae. Among the intra-alveolar and peri-bronchiolar lymphocyte infiltrates, human lung-resident (CD103 + ) CD8 + and CD4 + T cells were sequestered in epithelial (CD326 + ) lung niches and secreted granzyme B and perforin, suggesting anti-viral cytotoxic activity. Infected mice also mounted human IgG antibody responses to SARS-CoV-2 viral proteins. Hence, HIS-DRAGA mice showed unique advantages as a surrogate in vivo human model for studying SARS-CoV-2 immunopathological mechanisms and testing the safety and efficacy of candidate vaccines and therapeutics.
Sprache
Englisch
Identifikatoren
ISSN: 2164-5515
eISSN: 2164-554X
DOI: 10.1080/21645515.2022.2048622
Titel-ID: cdi_doaj_primary_oai_doaj_org_article_83496351106a4407b5580eca263c9f4a

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