Attenuated activation of pulmonary immune cells in mRNA-1273–vaccinated hamsters after SARS-CoV-2 infection

• Published in: The Journal of clinical investigation Vol. 131; no. 20; pp. 1 - 16
• Main Authors: Meyer, Michelle, Wang, Yuan, Edwards, Darin, Smith, Gregory R., Rubenstein, Aliza B., Ramanathan, Palaniappan, Mire, Chad E., Pietzsch, Colette, Chen, Xi, Ge, Yongchao, Cheng, Wan Sze, Henry, Carole, Woods, Angela, Ma, LingZhi, Stewart-Jones, Guillaume B.E., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Periasamy, Sivakumar, Shi, Pei-Yong, Graham, Barney S., Moore, Ian N., Ramos, Irene, Troyanskaya, Olga G., Zaslavsky, Elena, Carfi, Andrea, Sealfon, Stuart C., Bukreyev, Alexander
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.10.2021
• Subjects: 2019-nCoV Vaccine mRNA-1273; Animals; Antibodies; Antibodies, Neutralizing - biosynthesis; Antibodies, Viral - biosynthesis; Antiviral drugs; Biomedical research; Cell activation; Coronaviruses; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; COVID-19 Vaccines - pharmacology; Development and progression; Disease Models, Animal; Disease transmission; FDA approval; Female; Hamsters; Health aspects; Homeostasis; Humans; Immune response; Immunization, Secondary; Immunological research; Infections; Inflammation; Leukocytes; Lung - immunology; Lung - pathology; Lung - virology; Lung diseases; Lungs; Lymphocyte Activation; Lymphocytes; Mesocricetus; Messenger RNA; Physiological aspects; Prevention; Replication; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Single-Cell Analysis; Transcriptomes; Vaccines; Virus Replication; United States; Adaptive immunity; Immunology; Vaccines; Bioinformatics; Cellular immune response
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI148036

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.