mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
ABSTRACT The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
Sealfon Stuart C.、Meyer Michelle、Rubenstein Aliza B.、Ramanathan Palaniappan、Mire Chad E.、Ge Yongchao、Ma LingZhi、Stewart-Jones Guillaume B. E.、Shi Pei-Yong、Zaslavsky Elena、Graham Barney S.、Cheng Wan Sze、Bukreyev Alexander、Edwards Darin、Henry Carole、Smith Gregory R.、Minai Mahnaz、Chen Xi、Wang Yuan、Pietzsch Colette、Periasamy Sivakumar、Ramos Irene、Nagata Bianca M.、Moore Ian N.、Bock Kevin W.、Woods Angela、Carfi Andrea、Troyanskaya Olga G.
Department of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Pathology, University of Texas Medical Branch||Galveston National LaboratoryDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Pathology, University of Texas Medical Branch||Galveston National LaboratoryGalveston National Laboratory||Department of Microbiology & Immunology, University of Texas Medical BranchDepartment of Neurology, Icahn School of Medicine at Mount SinaiModerna IncModerna IncDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchDepartment of Neurology, Icahn School of Medicine at Mount SinaiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Pathology, University of Texas Medical Branch||Galveston National Laboratory||Department of Microbiology & Immunology, University of Texas Medical BranchModerna IncModerna IncDepartment of Neurology, Icahn School of Medicine at Mount SinaiInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLewis-Sigler Institute of Integrative Genomics, Princeton University||Center for Computational Biology, Flatiron InstituteDepartment of Computer Science, Princeton University||Lewis-Sigler Institute of Integrative Genomics, Princeton UniversityDepartment of Pathology, University of Texas Medical Branch||Galveston National LaboratoryDepartment of Pathology, University of Texas Medical Branch||Galveston National LaboratoryDepartment of Neurology, Icahn School of Medicine at Mount SinaiInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthModerna IncModerna IncDepartment of Computer Science, Princeton University||Lewis-Sigler Institute of Integrative Genomics, Princeton University||Center for Computational Biology, Flatiron Institute
医药卫生理论医学研究方法预防医学
Sealfon Stuart C.,Meyer Michelle,Rubenstein Aliza B.,Ramanathan Palaniappan,Mire Chad E.,Ge Yongchao,Ma LingZhi,Stewart-Jones Guillaume B. E.,Shi Pei-Yong,Zaslavsky Elena,Graham Barney S.,Cheng Wan Sze,Bukreyev Alexander,Edwards Darin,Henry Carole,Smith Gregory R.,Minai Mahnaz,Chen Xi,Wang Yuan,Pietzsch Colette,Periasamy Sivakumar,Ramos Irene,Nagata Bianca M.,Moore Ian N.,Bock Kevin W.,Woods Angela,Carfi Andrea,Troyanskaya Olga G..mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2021.01.25.428136.点此复制
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