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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.
Laczkó, Dorottya; Hogan, Michael J; Toulmin, Sushila A; Hicks, Philip; Lederer, Katlyn; Gaudette, Brian T; Castaño, Diana; Amanat, Fatima; Muramatsu, Hiromi; Oguin, Thomas H; Ojha, Amrita; Zhang, Lizhou; Mu, Zekun; Parks, Robert; Manzoni, Tomaz B; Roper, Brianne; Strohmeier, Shirin; Tombácz, István; Arwood, Leslee; Nachbagauer, Raffael; Karikó, Katalin; Greenhouse, Jack; Pessaint, Laurent; Porto, Maciel; Putman-Taylor, Tammy; Strasbaugh, Amanda; Campbell, Tracey-Ann; Lin, Paulo J C; Tam, Ying K; Sempowski, Gregory D; Farzan, Michael; Choe, Hyeryun; Saunders, Kevin O; Haynes, Barton F; Andersen, Hanne; Eisenlohr, Laurence C; Weissman, Drew; Krammer, Florian; Bates, Paul; Allman, David; Locci, Michela; Pardi, Norbert.
  • Laczkó D; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hogan MJ; Division of Protective Immunity, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
  • Toulmin SA; Division of Protective Immunity, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
  • Hicks P; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lederer K; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Gaudette BT; The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Castaño D; 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.
  • Amanat F; 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.
  • Muramatsu H; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Oguin TH; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Ojha A; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
  • Zhang L; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
  • Mu Z; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Parks R; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Manzoni TB; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Roper B; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Tombácz I; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Arwood L; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Karikó K; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; BioNTech RNA Pharmaceuticals, Mainz, Germany.
  • Greenhouse J; BIOQUAL Inc., Rockville, MD, USA.
  • Pessaint L; BIOQUAL Inc., Rockville, MD, USA.
  • Porto M; BIOQUAL Inc., Rockville, MD, USA.
  • Putman-Taylor T; BIOQUAL Inc., Rockville, MD, USA.
  • Strasbaugh A; BIOQUAL Inc., Rockville, MD, USA.
  • Campbell TA; BIOQUAL Inc., Rockville, MD, USA.
  • Lin PJC; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Tam YK; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Sempowski GD; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • Farzan M; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
  • Choe H; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
  • Saunders KO; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Haynes BF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Andersen H; BIOQUAL Inc., Rockville, MD, USA.
  • Eisenlohr LC; 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.
  • Weissman D; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bates P; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Allman D; The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Locci M; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Pardi N; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: pnorbert@pennmedicine.upenn.edu.
Immunity ; 53(4): 724-732.e7, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-710374
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / RNA, Messenger / RNA, Viral / Viral Vaccines / Coronavirus Infections / Antibodies, Neutralizing / Pandemics / Betacoronavirus / Antibodies, Viral Type of study: Experimental Studies Topics: Vaccines Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2020 Document Type: Article Affiliation country: J.immuni.2020.07.019

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / RNA, Messenger / RNA, Viral / Viral Vaccines / Coronavirus Infections / Antibodies, Neutralizing / Pandemics / Betacoronavirus / Antibodies, Viral Type of study: Experimental Studies Topics: Vaccines Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2020 Document Type: Article Affiliation country: J.immuni.2020.07.019