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Oligomeric state of the ZIKV E protein defines protective immune responses.
Metz, Stefan W; Thomas, Ashlie; Brackbill, Alex; Forsberg, John; Miley, Michael J; Lopez, Cesar A; Lazear, Helen M; Tian, Shaomin; de Silva, Aravinda M.
Afiliación
  • Metz SW; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. swmetz@med.unc.edu.
  • Thomas A; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Brackbill A; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Forsberg J; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Miley MJ; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lopez CA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lazear HM; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Tian S; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • de Silva AM; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. aravinda_desilva@med.unc.edu.
Nat Commun ; 10(1): 4606, 2019 10 10.
Article en En | MEDLINE | ID: mdl-31601808
The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas Virales / Proteínas del Envoltorio Viral / Virus Zika Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas Virales / Proteínas del Envoltorio Viral / Virus Zika Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido