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A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.
Immunity. 2020 10 13; 53(4):724-732.e7.I

Abstract

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

Authors+Show Affiliations

Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Division of Protective Immunity, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA.Division of Protective Immunity, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; BioNTech RNA Pharmaceuticals, Mainz, Germany.BIOQUAL Inc., Rockville, MD, USA.BIOQUAL Inc., Rockville, MD, USA.BIOQUAL Inc., Rockville, MD, USA.BIOQUAL Inc., Rockville, MD, USA.BIOQUAL Inc., Rockville, MD, USA.BIOQUAL Inc., Rockville, MD, USA.Acuitas Therapeutics, Vancouver, BC, Canada.Acuitas Therapeutics, Vancouver, BC, Canada.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA.Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.BIOQUAL Inc., Rockville, MD, USA.Division of Protective Immunity, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA; The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: pnorbert@pennmedicine.upenn.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32783919

Citation

Laczkó, Dorottya, et al. "A Single Immunization With Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses Against SARS-CoV-2 in Mice." Immunity, vol. 53, no. 4, 2020, pp. 724-732.e7.
Laczkó D, Hogan MJ, Toulmin SA, et al. A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice. Immunity. 2020;53(4):724-732.e7.
Laczkó, D., Hogan, M. J., Toulmin, S. A., Hicks, P., Lederer, K., Gaudette, B. T., Castaño, D., Amanat, F., Muramatsu, H., Oguin, T. H., Ojha, A., Zhang, L., Mu, Z., Parks, R., Manzoni, T. B., Roper, B., Strohmeier, S., Tombácz, I., Arwood, L., ... Pardi, N. (2020). A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice. Immunity, 53(4), 724-e7. https://doi.org/10.1016/j.immuni.2020.07.019
Laczkó D, et al. A Single Immunization With Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses Against SARS-CoV-2 in Mice. Immunity. 2020 10 13;53(4):724-732.e7. PubMed PMID: 32783919.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice. AU - Laczkó,Dorottya, AU - Hogan,Michael J, AU - Toulmin,Sushila A, AU - Hicks,Philip, AU - Lederer,Katlyn, AU - Gaudette,Brian T, AU - Castaño,Diana, AU - Amanat,Fatima, AU - Muramatsu,Hiromi, AU - Oguin,Thomas H,3rd AU - Ojha,Amrita, AU - Zhang,Lizhou, AU - Mu,Zekun, AU - Parks,Robert, AU - Manzoni,Tomaz B, AU - Roper,Brianne, AU - Strohmeier,Shirin, AU - Tombácz,István, AU - Arwood,Leslee, AU - Nachbagauer,Raffael, AU - Karikó,Katalin, AU - Greenhouse,Jack, AU - Pessaint,Laurent, AU - Porto,Maciel, AU - Putman-Taylor,Tammy, AU - Strasbaugh,Amanda, AU - Campbell,Tracey-Ann, AU - Lin,Paulo J C, AU - Tam,Ying K, AU - Sempowski,Gregory D, AU - Farzan,Michael, AU - Choe,Hyeryun, AU - Saunders,Kevin O, AU - Haynes,Barton F, AU - Andersen,Hanne, AU - Eisenlohr,Laurence C, AU - Weissman,Drew, AU - Krammer,Florian, AU - Bates,Paul, AU - Allman,David, AU - Locci,Michela, AU - Pardi,Norbert, Y1 - 2020/07/30/ PY - 2020/06/17/received PY - 2020/07/16/revised PY - 2020/07/23/accepted PY - 2020/8/14/pubmed PY - 2020/10/29/medline PY - 2020/8/14/entrez KW - COVID-19 KW - SARS-CoV-2 KW - mRNA vaccine KW - mRNA-LNP KW - nucleoside-modified mRNA SP - 724 EP - 732.e7 JF - Immunity JO - Immunity VL - 53 IS - 4 N2 - SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19. SN - 1097-4180 UR - https://www.unboundmedicine.com/medline/citation/32783919/A_Single_Immunization_with_Nucleoside_Modified_mRNA_Vaccines_Elicits_Strong_Cellular_and_Humoral_Immune_Responses_against_SARS_CoV_2_in_Mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7613(20)30326-5 DB - PRIME DP - Unbound Medicine ER -