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A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity

Author

Listed:
  • Ellen Young

    (University of North Carolina)

  • Boyd Yount

    (University of North Carolina)

  • Petraleigh Pantoja

    (University of Puerto Rico-Medical Sciences Campus)

  • Sandra Henein

    (University of North Carolina)

  • Rita M. Meganck

    (Saint Louis University)

  • Jennifer McBride

    (University of North Carolina)

  • Jennifer E. Munt

    (University of North Carolina)

  • Thomas J. Baric

    (University of North Carolina)

  • Deanna Zhu

    (University of North Carolina)

  • Trevor Scobey

    (University of North Carolina)

  • Stephanie Dong

    (University of North Carolina)

  • Longping V. Tse

    (Saint Louis University)

  • Melween I. Martinez

    (University of Puerto Rico-Medical Sciences Campus)

  • Armando G. Burgos

    (University of Puerto Rico-Medical Sciences Campus)

  • Rachel L. Graham

    (University of North Carolina)

  • Laura White

    (University of North Carolina)

  • Aravinda DeSilva

    (University of North Carolina)

  • Carlos A. Sariol

    (University of Puerto Rico-Medical Sciences Campus
    University of Puerto Rico-Medical Sciences Campus
    University of Puerto Rico-Medical Sciences Campus
    University of Puerto Rico-Medical Sciences Campus)

  • Ralph S. Baric

    (University of North Carolina
    University of North Carolina)

Abstract

The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective immunity. Among the number of vaccine candidates in clinical trials, only Dengvaxia is licensed for use in DENV seropositive individuals. To simplify live-virus vaccine design, we identify co-evolutionary constraints inherent in flavivirus virion assembly and design chimeric viruses to replace domain II (EDII) of the DENV2 envelope (E) glycoprotein with EDII from DENV4. The chimeric DENV2/4EDII virus replicates efficiently in vitro and in vivo. In male macaques, a single inoculation of DENV2/4EDII induces type-specific neutralizing antibodies to both DENV2 and DENV4, thereby providing a strategy to simplify DENV vaccine design by utilizing a single bivalent E glycoprotein immunogen for two DENV serotypes.

Suggested Citation

  • Ellen Young & Boyd Yount & Petraleigh Pantoja & Sandra Henein & Rita M. Meganck & Jennifer McBride & Jennifer E. Munt & Thomas J. Baric & Deanna Zhu & Trevor Scobey & Stephanie Dong & Longping V. Tse , 2023. "A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36702-x
    DOI: 10.1038/s41467-023-36702-x
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    References listed on IDEAS

    as
    1. Samir Bhatt & Peter W. Gething & Oliver J. Brady & Jane P. Messina & Andrew W. Farlow & Catherine L. Moyes & John M. Drake & John S. Brownstein & Anne G. Hoen & Osman Sankoh & Monica F. Myers & Dylan , 2013. "The global distribution and burden of dengue," Nature, Nature, vol. 496(7446), pages 504-507, April.
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