Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model.

Following the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread throughout the world, new viral variants of concern (VOC) have emerged. There is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. Syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (COVID-19). We performed intranasal inoculation of SARS-CoV-2 into hamsters with the ancestral virus (nCoV-WA1-2020) or VOC first identified in the United Kingdom (B.1.1.7, alpha) and South Africa (B.1.351, beta) and analyzed viral loads and host responses. Similar gross and histopathologic pulmonary lesions were observed after infection with all three variants. Although differences in viral genomic copy numbers were noted in the lungs and oral swabs of challenged animals, infectious titers in the lungs were comparable between the variants. Antibody neutralization capacities varied, dependent on the original challenge virus and cross-variant protective capacity. Transcriptional profiling of lung samples 4 days post-challenge (DPC) indicated significant induction of antiviral pathways in response to all three challenges with a more robust inflammatory signature in response to B.1.1.7 infection. Furthermore, no additional mutations in the spike protein were detected at 4 DPC. Although disease severity and viral shedding were not significantly different, the emerging VOC induced distinct humoral responses and transcriptional profiles compared to the ancestral virus. These observations suggest potential differences in acute early responses or alterations in immune modulation by VOC. Intramural Research Program, NIAID, NIH; National Center for Research Resources, NIH; National Center for Advancing Translational Sciences, NIH.

O'Donnell KL ，Pinski AN ，Clancy CS ，Gourdine T ，Shifflett K ，Fletcher P ，Messaoudi I ，Marzi A ... -  《EBioMedicine》

Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model.

O'Donnell KL ，Pinski AN ，Clancy CS ，Gourdine T ，Shifflett K ，Fletcher P ，Messaoudi I ，Marzi A ... -  《-》

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model.

Dhakal S ，Ruiz-Bedoya CA ，Zhou R ，Creisher PS ，Villano JS ，Littlefield K ，Ruelas Castillo J ，Marinho P ，Jedlicka AE ，Ordonez AA ，Bahr M ，Majewska N ，Betenbaugh MJ ，Flavahan K ，Mueller ARL ，Looney MM ，Quijada D ，Mota F ，Beck SE ，Brockhurst J ，Braxton AM ，Castell N ，Stover M ，D'Alessio FR ，Metcalf Pate KA ，Karakousis PC ，Mankowski JL ，Pekosz A ，Jain SK ，Klein SL ，Johns Hopkins COVID-19 Hamster Study Group ... -  《mBio》

SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern.

Hawman DW ，Meade-White K ，Archer J ，Leventhal SS ，Wilson D ，Shaia C ，Randall S ，Khandhar AP ，Krieger K ，Hsiang TY ，Gale M ，Berglund P ，Fuller DH ，Feldmann H ，Erasmus JH ... -  《eLife》

Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines-A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters.

Trimpert J ，Herwig S ，Stein J ，Vladimirova D ，Adler JM ，Abdelgawad A ，Firsching TC ，Thoma T ，Sehouli J ，Osterrieder K ，Gruber AD ，Sawitzki B ，Sander LE ，Cichon G ... -  《Viruses-Basel》