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Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles.
Melo, Mariane; Porter, Ely; Zhang, Yuan; Silva, Murillo; Li, Na; Dobosh, Brian; Liguori, Alessia; Skog, Pat; Landais, Elise; Menis, Sergey; Sok, Devin; Nemazee, David; Schief, William R; Weiss, Ron; Irvine, Darrell J.
Afiliación
  • Melo M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Porter E; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Zhang Y; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Silva M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.
  • Li N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.
  • Dobosh B; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Liguori A; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Skog P; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Landais E; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Menis S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Sok D; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Nemazee D; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
  • Schief WR; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Har
  • Weiss R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Irvine DJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Bi
Mol Ther ; 27(12): 2080-2090, 2019 12 04.
Article en En | MEDLINE | ID: mdl-31515132
RNA replicons are a promising platform technology for vaccines. To evaluate the potential of lipid nanoparticle-formulated replicons for delivery of HIV immunogens, we designed and tested an alphavirus replicon expressing a self-assembling protein nanoparticle immunogen, the glycoprotein 120 (gp120) germline-targeting engineered outer domain (eOD-GT8) 60-mer. The eOD-GT8 immunogen is a germline-targeting antigen designed to prime human B cells capable of evolving toward VRC01-class broadly neutralizing antibodies. Replicon RNA was encapsulated with high efficiency in 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based lipid nanoparticles, which provided effective delivery in the muscle and expression of luciferase lasting ∼30 days in normal mice, contrasting with very brief and low levels of expression obtained by delivery of equivalent modified mRNA (modRNA). eOD-GT8 60-mer-encoding replicons elicited high titers of gp120-specific antibodies following a single injection in mice, and increased levels of antigen-specific germinal center B cells compared with protein immunization. Immunization of transgenic mice expressing human inferred-germline VRC01 heavy chain B cell receptors that are the targets of the eOD antigen led to priming of B cells and somatic hypermutation consistent with VRC01-class antibody development. Altogether, these data suggest replicon delivery of Env immunogens may be a promising avenue for HIV vaccine development.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Replicón / Anticuerpos Anti-VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Nanopartículas / Productos del Gen env del Virus de la Inmunodeficiencia Humana Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Replicón / Anticuerpos Anti-VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Nanopartículas / Productos del Gen env del Virus de la Inmunodeficiencia Humana Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos