Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection.
Michelle Meyer, Yuan Wang, Darin Edwards, Gregory R Smith, Aliza B Rubenstein, Palaniappan Ramanathan, Chad E Mire, Colette Pietzsch, Xi Chen, Yongchao Ge, Wan Sze Cheng, Carole Henry, Angela Woods, LingZhi Ma, Guillaume Be Stewart-Jones, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, Sivakumar Periasamy, Pei-Yong Shi, Barney S Graham, Ian N Moore, Irene Ramos, Olga G Troyanskaya, Elena Zaslavsky, Andrea Carfi, Stuart C Sealfon, Alexander Bukreyev
Author Information
Michelle Meyer: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Yuan Wang: Department of Computer Science and.
Darin Edwards: Moderna Inc., Cambridge, Massachusetts, USA.
Gregory R Smith: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Aliza B Rubenstein: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Palaniappan Ramanathan: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Chad E Mire: Galveston National Laboratory, Galveston, Texas, USA.
Colette Pietzsch: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Xi Chen: Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
Yongchao Ge: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Wan Sze Cheng: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Carole Henry: Moderna Inc., Cambridge, Massachusetts, USA.
Angela Woods: Moderna Inc., Cambridge, Massachusetts, USA.
LingZhi Ma: Moderna Inc., Cambridge, Massachusetts, USA.
Guillaume Be Stewart-Jones: Moderna Inc., Cambridge, Massachusetts, USA.
Kevin W Bock: Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Mahnaz Minai: Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Bianca M Nagata: Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Sivakumar Periasamy: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Pei-Yong Shi: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Barney S Graham: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Ian N Moore: Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Irene Ramos: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Olga G Troyanskaya: Department of Computer Science and.
Elena Zaslavsky: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Andrea Carfi: Moderna Inc., Cambridge, Massachusetts, USA.
Stuart C Sealfon: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Alexander Bukreyev: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
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.
