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Michelle Meyer, … , Stuart C. Sealfon, Alexander Bukreyev
Published August 27, 2021
Citation Information: J Clin Invest. 2021;131(20):e148036. https://doi.org/10.1172/JCI148036.
Citation Information: J Clin Invest. 2021;131(20):e148036. https://doi.org/10.1172/JCI148036.
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.
Authors
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 B.E. 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
Citation information
Citations to this article (27)
| Title and authors | Publication | Year |
|---|---|---|
|
Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation
Alok K Singh, Rulin Wang, Kara A Lombardo, Monali Praharaj, C Korin Bullen, Peter Um, Stephanie Davis, Oliver Komm, Peter B Illei, Alvaro A Ordonez, Melissa Bahr, Joy Huang, Anuj Gupta, Kevin J Psoter, Sanjay K Jain, Trinity J Bivalacqua, Srinivasan Yegnasubramanian, William R Bishai |
||
|
Differential efficacy of first licensed western vaccines protecting without immunopathogenesis Wuhan-1-challenged hamsters from severe COVID-19
Ebenig A, Lange MV, Gellhorn Serra M, Kupke A, Plesker R, Qu B, Brown RJ, Maier TJ, Mühlebach MD |
NPJ Vaccines | 2025 |
|
Tapioca: a platform for predicting de novo protein-protein interactions in dynamic contexts.
Reed TJ, Tyl MD, Tadych A, Troyanskaya OG, Cristea IM, Reed TJ, Tyl MD, Tadych A, Troyanskaya OG, Cristea IM |
Nature Methods | 2024 |
|
Lipid nanoparticle encapsulation of a Delta spike-CD40L DNA vaccine improves effectiveness against Omicron challenge in Syrian hamsters
Tamming L, Duque D, Tran A, Lansdell C, Frahm G, Wu J, Fekete EE, Creskey M, Thulasi Raman SN, Laryea E, Zhang W, Pfeifle A, Gravel C, Stalker A, Hashem AM, Chen W, Stuible M, Durocher Y, Safronetz D, Cao J, Wang L, Sauve S, Rosu-Myles M, Zhang X, Johnston MJ, Li X |
Molecular Therapy. Methods & Clinical Development | 2024 |
|
Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine
Wee EG, Kempster S, Ferguson D, Hall J, Ham C, Morris S, Crook A, Gilbert SC, Korber B, Almond N, Hanke T |
Vaccines | 2024 |
|
A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models
Warner NL, Archer J, Park S, Singh G, McFadden KM, Kimura T, Nicholes K, Simpson A, Kaelber JT, Hawman DW, Feldmann H, Khandhar AP, Berglund P, Vogt MR, Erasmus JH |
Science translational medicine | 2024 |
|
PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer.
Gao S, Zhang W, Ma J, Ni X |
Journal of Translational Medicine | 2023 |
|
Mechanisms driving the immunoregulatory function of cancer cells.
van Weverwijk A, de Visser KE |
Nature reviews. Cancer | 2023 |
|
Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy
Yang L, Chu Z, Liu M, Zou Q, Li J, Liu Q, Wang Y, Wang T, Xiang J, Wang B |
Journal of Hematology & Oncology | 2023 |
|
Understanding virus-host interactions in tissues.
Speranza E |
Nature Microbiology | 2023 |
|
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Baldeon Vaca G, Meyer M, Cadete A, Hsiao CJ, Golding A, Jeon A, Jacquinet E, Azcue E, Guan CM, Sanchez-Felix X, Pietzsch CA, Mire CE, Hyde MA, Comeaux ME, Williams JM, Sung JC, Carfi A, Edwards DK, Bukreyev A, Bahl K |
Science Advances | 2023 |
|
A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models
G Maruggi, C Mallett, J Westerbeck, T Chen, G Lofano, K Friedrich, L Qu, J Sun, J McAuliffe, A Kanitkar, K Arrildt, K Wang, I McBee, D McCoy, R Terry, A Rowles, M Abrahim, M Ringenberg, M Gains, C Spickler, X Xie, J Zou, P Shi, T Dutt, M Henao-Tamayo, I Ragan, R Bowen, R Johnson, S Nuti, K Luisi, J Ulmer, A Steff, R Jalah, S Bertholet, A Stokes, D Yu |
Molecular Therapy | 2022 |
|
A self-amplifying RNA vaccine protects against SARS-CoV-2 (D614G) and Alpha variant of concern (B.1.1.7) in a transmission-challenge hamster model
R Frise, L Baillon, J Zhou, R Kugathasan, T Peacock, J Brown, K Samnuan, P McKay, R Shattock, W Barclay |
Vaccine | 2022 |
|
SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
D Hawman, K Meade-White, J Archer, S Leventhal, D Wilson, C Shaia, S Randall, A Khandhar, K Krieger, T Hsiang, M Gale, P Berglund, D Fuller, H Feldmann, J Erasmus |
eLife | 2022 |
|
Intranasal immunization with avian paramyxovirus type 3 expressing SARS-CoV-2 spike protein protects hamsters against SARS-CoV-2.
Park HS, Matsuoka Y, Luongo C, Yang L, Santos C, Liu X, Ahlers LRH, Moore IN, Afroz S, Johnson RF, Lafont BAP, Dorward DW, Fischer ER, Martens C, Samal SK, Munir S, Buchholz UJ, Le Nouën C |
npj Vaccines | 2022 |
|
Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment
Ma G, Zhang Z, Li P, Zhang Z, Zeng M, Liang Z, Li D, Wang L, Chen Y, Liang Y, Niu H |
Cell communication and signaling : CCS | 2022 |
|
A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2
Ilinykh PA, Periasamy S, Huang K, Kuzmina NA, Ramanathan P, Meyer MN, Mire CE, Kuzmin IV, Bharaj P, Endsley JR, Chikina M, Sealfon SC, Widen SG, Endsley MA, Bukreyev A |
npj Vaccines | 2022 |
|
Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19
Blanas A, Karsjens H, de Ligt A, Huijbers EJ, van Loon K, Denisov SS, Durukan C, Engbersen DJ, Groen J, Hennig S, Hackeng TM, van Beijnum JR, Griffioen AW |
iScience | 2022 |
|
Delineating COVID-19 immunological features using single-cell RNA sequencing
Liu W, Jia J, Dai Y, Chen W, Pei G, Yan Q, Zhao Z |
2022 | |
|
Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function.
Ping Y, Shan J, Liu Y, Liu F, Wang L, Liu Z, Li J, Yue D, Wang L, Chen X, Zhang Y |
Cancer Immunology, Immunotherapy | 2022 |
|
Animal models for studying coronavirus infections and developing antiviral agents and vaccines.
Lin Q, Lu C, Hong Y, Li R, Chen J, Chen W, Chen J |
Antiviral Research | 2022 |
|
Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models
Hajnik RL, Plante JA, Liang Y, Alameh MG, Tang J, Bonam SR, Zhong C, Adam A, Scharton D, Rafael GH, Liu Y, Hazell NC, Sun J, Soong L, Shi PY, Wang T, Walker DH, Sun J, Weissman D, Weaver SC, Plante KS, Hu H |
Science Translational Medicine | 2022 |
|
Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection.
Li Q, Vijaykumar K, Philips SE, Hussain SS, Huynh VN, Fernandez-Petty CM, Lever JEP, Foote JB, Ren J, Campos-Gómez J, Daya FA, Hubbs NW, Kim H, Onuoha E, Boitet ER, Fu L, Leung HM, Yu L, Detchemendy TW, Schaefers LT, Tipper JL, Edwards LJ, Leal SM Jr, Harrod KS, Tearney GJ, Rowe SM |
bioRxiv : the preprint server for biology | 2022 |
|
Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation
Singh AK, Wang R, Lombardo KA, Praharaj M, Bullen CK, Um P, Davis S, Komm O, Illei PB, Ordonez AA, Bahr M, Huang J, Gupta A, Psoter KJ, Jain SK, Bivalacqua TJ, Yegnasubramanian S, Bishai WR |
2022 | |
|
Influenza Virus and SARS-CoV-2 Vaccines
A Sandor, M Sturdivant, J Ting |
Journal of immunology (Baltimore, Md. : 1950) | 2021 |
|
The pivotal roles of the host immune response in the fine-tuning the infection and the development of the vaccines for SARS-CoV-2
W Alturaiki, A Mubarak, AA Jurayyan, MG Hemida |
Human Vaccines & Immunotherapeutics | 2021 |
|
SARS-CoV2 variant-specific replicating RNA vaccines protect from disease and pathology and reduce viral shedding following challenge with heterologous SARS-CoV2 variants of concern
Hawman DW, Meade-White K, Archer J, Leventhal S, Wilson D, Shaia C, Randall S, Khandhar AP, Hsiang TY, Gale M Jr, Berglund P, Fuller DH, Feldmann H, Erasmus JH |
2021 |
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