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A systematic approach to the development of a safe live attenuated Zika vaccine

Author

Listed:
  • Swee Sen Kwek

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Satoru Watanabe

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Kuan Rong Chan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Eugenia Z. Ong

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Hwee Cheng Tan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Wy Ching Ng

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Mien T. X. Nguyen

    (Programme in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School)

  • Esther S. Gan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Summer L. Zhang

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Kitti W. K. Chan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School
    National University of Singapore)

  • Jun Hao Tan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • October M. Sessions

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Menchie Manuel

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School)

  • Julien Pompon

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School
    MIVEGEC, IRD, CNRS, Univ. Montpellier)

  • Camillus Chua

    (SingHealth Translational Immunology and Inflammation Centre, SingHealth)

  • Sharifah Hazirah

    (SingHealth Translational Immunology and Inflammation Centre, SingHealth)

  • Karl Tryggvason

    (Programme in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School
    Karolinska Institute)

  • Subhash G. Vasudevan

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School
    National University of Singapore)

  • Eng Eong Ooi

    (Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School
    National University of Singapore
    Saw Swee Hock School of Public Health, National University of Singapore
    Singapore-MIT Alliance for Research and Technology, Infectious Diseases Interdisciplinary Group)

Abstract

Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.

Suggested Citation

  • Swee Sen Kwek & Satoru Watanabe & Kuan Rong Chan & Eugenia Z. Ong & Hwee Cheng Tan & Wy Ching Ng & Mien T. X. Nguyen & Esther S. Gan & Summer L. Zhang & Kitti W. K. Chan & Jun Hao Tan & October M. Ses, 2018. "A systematic approach to the development of a safe live attenuated Zika vaccine," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03337-2
    DOI: 10.1038/s41467-018-03337-2
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