TY - JOUR
T1 - Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection
AU - Meyer, Michelle
AU - Wang, Yuan
AU - Edwards, Darin
AU - Smith, Gregory R.
AU - Rubenstein, Aliza B.
AU - Ramanathan, Palaniappan
AU - Mire, Chad E.
AU - Pietzsch, Colette
AU - Chen, Xi
AU - Ge, Yongchao
AU - Cheng, Wan Sze
AU - Henry, Carole
AU - Woods, Angela
AU - Ma, Ling Zhi
AU - Stewart-Jones, Guillaume B.E.
AU - Bock, Kevin W.
AU - Minai, Mahnaz
AU - Nagata, Bianca M.
AU - Periasamy, Sivakumar
AU - Shi, Pei Yong
AU - Graham, Barney S.
AU - Moore, Ian N.
AU - Ramos, Irene
AU - Troyanskaya, Olga G.
AU - Zaslavsky, Elena
AU - Carfi, Andrea
AU - Sealfon, Stuart C.
AU - Bukreyev, Alexander
N1 - Publisher Copyright:
© 2021 American Society for Clinical Investigation. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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 SARSCoV- 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.
AB - 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 SARSCoV- 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.
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U2 - 10.1172/JCI148036
DO - 10.1172/JCI148036
M3 - Article
C2 - 34449440
AN - SCOPUS:85118265834
SN - 0021-9738
VL - 131
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 20
M1 - e148036
ER -