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Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.
Pardi, Norbert; Hogan, Michael J; Naradikian, Martin S; Parkhouse, Kaela; Cain, Derek W; Jones, Letitia; Moody, M Anthony; Verkerke, Hans P; Myles, Arpita; Willis, Elinor; LaBranche, Celia C; Montefiori, David C; Lobby, Jenna L; Saunders, Kevin O; Liao, Hua-Xin; Korber, Bette T; Sutherland, Laura L; Scearce, Richard M; Hraber, Peter T; Tombácz, István; Muramatsu, Hiromi; Ni, Houping; Balikov, Daniel A; Li, Charles; Mui, Barbara L; Tam, Ying K; Krammer, Florian; Karikó, Katalin; Polacino, Patricia; Eisenlohr, Laurence C; Madden, Thomas D; Hope, Michael J; Lewis, Mark G; Lee, Kelly K; Hu, Shiu-Lok; Hensley, Scott E; Cancro, Michael P; Haynes, Barton F; Weissman, Drew.
Afiliación
  • Pardi N; Department of Medicine, University of Pennsylvania, Philadelphia, PA pnorbert@pennmedicine.upenn.edu.
  • Hogan MJ; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Naradikian MS; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
  • Parkhouse K; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Cain DW; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Jones L; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Moody MA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Verkerke HP; Department of Medicinal Chemistry, University of Washington, Seattle, WA.
  • Myles A; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
  • Willis E; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • LaBranche CC; Department of Surgery, Duke University Medical Center, Durham, NC.
  • Montefiori DC; Department of Surgery, Duke University Medical Center, Durham, NC.
  • Lobby JL; Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, PA.
  • Saunders KO; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Liao HX; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Korber BT; Los Alamos National Laboratory, Los Alamos, NM.
  • Sutherland LL; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Scearce RM; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
  • Hraber PT; Los Alamos National Laboratory, Los Alamos, NM.
  • Tombácz I; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Muramatsu H; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Ni H; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Balikov DA; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Li C; Department of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Mui BL; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Tam YK; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Karikó K; BioNTech RNA Pharmaceuticals, Mainz, Germany.
  • Polacino P; Washington National Primate Research Center, University of Washington, Seattle, WA.
  • Eisenlohr LC; Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, PA.
  • Madden TD; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Hope MJ; Acuitas Therapeutics, Vancouver, BC, Canada.
  • Lewis MG; Bioqual Inc., Rockville, MD.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA.
  • Hu SL; Washington National Primate Research Center, University of Washington, Seattle, WA.
  • Hensley SE; Department of Pharmaceutics, University of Washington, Seattle, WA.
  • Cancro MP; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Haynes BF; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
  • Weissman D; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC.
J Exp Med ; 215(6): 1571-1588, 2018 06 04.
Article en En | MEDLINE | ID: mdl-29739835
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Linfocitos B / Linfocitos T Colaboradores-Inductores / Centro Germinal / Vacunas de Subunidad / Nucleósidos Límite: Animals Idioma: En Revista: J Exp Med Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Linfocitos B / Linfocitos T Colaboradores-Inductores / Centro Germinal / Vacunas de Subunidad / Nucleósidos Límite: Animals Idioma: En Revista: J Exp Med Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos