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Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2021 Oct 15; Vol. 131 (20). - Publication Year :
- 2021
-
Abstract
- The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical 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 exhibits severe SARS-CoV-2 disease similar to that in 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 nonhuman primates, low-level virus replication in mRNA-1273-vaccinated hamsters coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high-resolution analysis that 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 2-dose schedule and provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
- Subjects :
- 2019-nCoV Vaccine mRNA-1273
Animals
Antibodies, Neutralizing biosynthesis
Antibodies, Viral biosynthesis
COVID-19 virology
COVID-19 Vaccines administration & dosage
COVID-19 Vaccines immunology
Disease Models, Animal
Female
Humans
Immunization, Secondary
Lung pathology
Lung virology
Lymphocyte Activation
Mesocricetus
Single-Cell Analysis
Virus Replication
COVID-19 immunology
COVID-19 prevention & control
COVID-19 Vaccines pharmacology
Lung immunology
SARS-CoV-2 immunology
SARS-CoV-2 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 131
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 34449440
- Full Text :
- https://doi.org/10.1172/JCI148036