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Oligomeric state of the ZIKV E protein defines protective immune responses

Author

Listed:
  • Stefan W. Metz

    (University of North Carolina at Chapel Hill)

  • Ashlie Thomas

    (University of North Carolina at Chapel Hill)

  • Alex Brackbill

    (University of North Carolina at Chapel Hill)

  • John Forsberg

    (University of North Carolina at Chapel Hill)

  • Michael J. Miley

    (University of North Carolina at Chapel Hill)

  • Cesar A. Lopez

    (University of North Carolina at Chapel Hill)

  • Helen M. Lazear

    (University of North Carolina at Chapel Hill)

  • Shaomin Tian

    (University of North Carolina at Chapel Hill)

  • Aravinda M. de Silva

    (University of North Carolina at Chapel Hill)

Abstract

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.

Suggested Citation

  • Stefan W. Metz & Ashlie Thomas & Alex Brackbill & John Forsberg & Michael J. Miley & Cesar A. Lopez & Helen M. Lazear & Shaomin Tian & Aravinda M. de Silva, 2019. "Oligomeric state of the ZIKV E protein defines protective immune responses," Nature Communications, Nature, vol. 10(1), pages 1-7, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12677-6
    DOI: 10.1038/s41467-019-12677-6
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    Cited by:

    1. Kwinten Sliepen & Laura Radić & Joan Capella-Pujol & Yasunori Watanabe & Ian Zon & Ana Chumbe & Wen-Hsin Lee & Marlon Gast & Jelle Koopsen & Sylvie Koekkoek & Iván Moral-Sánchez & Philip J. M. Brouwer, 2022. "Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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