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Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.
Metz, Stefan W; Tian, Shaomin; Hoekstra, Gabriel; Yi, Xianwen; Stone, Michelle; Horvath, Katie; Miley, Michael J; DeSimone, Joseph; Luft, Chris J; de Silva, Aravinda M.
Afiliación
  • Metz SW; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Tian S; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Hoekstra G; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Yi X; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Stone M; Liquidia Technologies, Research Triangle Park, North Carolina, United States of America.
  • Horvath K; Liquidia Technologies, Research Triangle Park, North Carolina, United States of America.
  • Miley MJ; Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • DeSimone J; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Luft CJ; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • de Silva AM; Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, United States of America.
PLoS Negl Trop Dis ; 10(10): e0005071, 2016 Oct.
Article en En | MEDLINE | ID: mdl-27764114
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Envoltorio Viral / Virus del Dengue / Vacunas contra el Dengue / Nanopartículas / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Envoltorio Viral / Virus del Dengue / Vacunas contra el Dengue / Nanopartículas / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos