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Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever

Author

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  • Tiago Abreu-Mota

    (Sidney Kimmel Medical College at Thomas Jefferson University
    School of Medicine, University of Minho
    PT Government Associate Laboratory)

  • Katie R. Hagen

    (National Institutes of Health)

  • Kurt Cooper

    (National Institutes of Health)

  • Peter B. Jahrling

    (National Institutes of Health
    National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Gene Tan

    (Infectious Disease, The J. Craig Venter Institute
    University of California)

  • Christoph Wirblich

    (Sidney Kimmel Medical College at Thomas Jefferson University)

  • Reed F. Johnson

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Matthias J. Schnell

    (Sidney Kimmel Medical College at Thomas Jefferson University
    Sidney Kimmel Medical College at Thomas Jefferson University)

Abstract

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.

Suggested Citation

  • Tiago Abreu-Mota & Katie R. Hagen & Kurt Cooper & Peter B. Jahrling & Gene Tan & Christoph Wirblich & Reed F. Johnson & Matthias J. Schnell, 2018. "Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06741-w
    DOI: 10.1038/s41467-018-06741-w
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    Cited by:

    1. Mathieu Mateo & Stéphanie Reynard & Natalia Pietrosemoli & Emeline Perthame & Alexandra Journeaux & Kodie Noy & Clara Germain & Xavier Carnec & Caroline Picard & Virginie Borges-Cardoso & Jimmy Hortio, 2023. "Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Adam J. Ronk & Nicole M. Lloyd & Min Zhang & Caroline Atyeo & Hailee R. Perrett & Chad E. Mire & Kathryn M. Hastie & Rogier W. Sanders & Philip J. M. Brouwer & Erica Olmann Saphire & Andrew B. Ward & , 2023. "A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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