tetano
Editor, Senior Moderator
J Clin Invest
. 2021 Aug 27;148036.
doi: 10.1172/JCI148036. Online ahead of print.
Attenuated activation of pulmonary immune cells in mRNA-1273 vaccinated hamsters after SARS-CoV-2 infection
Michelle Meyer[SUP] 1 [/SUP], Yuan Wang[SUP] 2 [/SUP], Darin Edwards[SUP] 3 [/SUP], Gregory R Smith[SUP] 4 [/SUP], Aliza B Rubenstein[SUP] 4 [/SUP], Palaniappan Ramanathan[SUP] 1 [/SUP], Chad E Mire[SUP] 5 [/SUP], Colette Pietzsch[SUP] 1 [/SUP], Xi Chen[SUP] 2 [/SUP], Yongchao Ge[SUP] 4 [/SUP], Wan Sze Cheng[SUP] 4 [/SUP], Carole Henry[SUP] 3 [/SUP], Angela Woods[SUP] 3 [/SUP], LingZhi Ma[SUP] 3 [/SUP], Guillaume Be Stewart-Jones[SUP] 3 [/SUP], Kevin W Bock[SUP] 6 [/SUP], Mahnaz Minai[SUP] 7 [/SUP], Bianca M Nagata[SUP] 8 [/SUP], Sivakumar Periasamy[SUP] 1 [/SUP], Pei-Yong Shi[SUP] 9 [/SUP], Barney S Graham[SUP] 7 [/SUP], Ian N Moore[SUP] 10 [/SUP], Irene Ramos[SUP] 4 [/SUP], Olga G Troyanskaya[SUP] 2 [/SUP], Elena Zaslavsky[SUP] 4 [/SUP], Andrea Carfi[SUP] 3 [/SUP], Stuart C Sealfon[SUP] 4 [/SUP], Alexander Bukreyev[SUP] 1 [/SUP]
Affiliations
Abstract
The mRNA-1273 vaccine is effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was granted emergency use authorization by the Food and Drug Administration . 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 exhibit 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, 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 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 provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
Keywords: Adaptive immunity; Bioinformatics; Cellular immune response; Immunology; Vaccines.
. 2021 Aug 27;148036.
doi: 10.1172/JCI148036. Online ahead of print.
Attenuated activation of pulmonary immune cells in mRNA-1273 vaccinated hamsters after SARS-CoV-2 infection
Michelle Meyer[SUP] 1 [/SUP], Yuan Wang[SUP] 2 [/SUP], Darin Edwards[SUP] 3 [/SUP], Gregory R Smith[SUP] 4 [/SUP], Aliza B Rubenstein[SUP] 4 [/SUP], Palaniappan Ramanathan[SUP] 1 [/SUP], Chad E Mire[SUP] 5 [/SUP], Colette Pietzsch[SUP] 1 [/SUP], Xi Chen[SUP] 2 [/SUP], Yongchao Ge[SUP] 4 [/SUP], Wan Sze Cheng[SUP] 4 [/SUP], Carole Henry[SUP] 3 [/SUP], Angela Woods[SUP] 3 [/SUP], LingZhi Ma[SUP] 3 [/SUP], Guillaume Be Stewart-Jones[SUP] 3 [/SUP], Kevin W Bock[SUP] 6 [/SUP], Mahnaz Minai[SUP] 7 [/SUP], Bianca M Nagata[SUP] 8 [/SUP], Sivakumar Periasamy[SUP] 1 [/SUP], Pei-Yong Shi[SUP] 9 [/SUP], Barney S Graham[SUP] 7 [/SUP], Ian N Moore[SUP] 10 [/SUP], Irene Ramos[SUP] 4 [/SUP], Olga G Troyanskaya[SUP] 2 [/SUP], Elena Zaslavsky[SUP] 4 [/SUP], Andrea Carfi[SUP] 3 [/SUP], Stuart C Sealfon[SUP] 4 [/SUP], Alexander Bukreyev[SUP] 1 [/SUP]
Affiliations
- PMID: 34449440
- DOI: 10.1172/JCI148036
Abstract
The mRNA-1273 vaccine is effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was granted emergency use authorization by the Food and Drug Administration . 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 exhibit 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, 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 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 provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
Keywords: Adaptive immunity; Bioinformatics; Cellular immune response; Immunology; Vaccines.