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A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Author

Listed:
  • Adam J. Ronk

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Nicole M. Lloyd

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Min Zhang

    (University of Texas Medical Branch)

  • Caroline Atyeo

    (Harvard T.H. Chan School of Public Health)

  • Hailee R. Perrett

    (Department of Integrative Structural and Computational Biology California Campus, Scripps Research)

  • Chad E. Mire

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Kathryn M. Hastie

    (La Jolla Institute for Immunology)

  • Rogier W. Sanders

    (Academic Medical Center)

  • Philip J. M. Brouwer

    (Academic Medical Center)

  • Erica Olmann Saphire

    (La Jolla Institute for Immunology)

  • Andrew B. Ward

    (Department of Integrative Structural and Computational Biology California Campus, Scripps Research)

  • Thomas G. Ksiazek

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Juan Carlos Alvarez Moreno

    (University of Texas Medical Branch)

  • Harshwardhan M. Thaker

    (University of Texas Medical Branch)

  • Galit Alter

    (Harvard T.H. Chan School of Public Health)

  • Sunny Himansu

    (Moderna, Inc)

  • Andrea Carfi

    (Moderna, Inc)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

Abstract

Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41376-6
    DOI: 10.1038/s41467-023-41376-6
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    References listed on IDEAS

    as
    1. 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.
    2. James E. Robinson & Kathryn M. Hastie & Robert W. Cross & Rachael E. Yenni & Deborah H. Elliott & Julie A. Rouelle & Chandrika B. Kannadka & Ashley A. Smira & Courtney E. Garry & Benjamin T. Bradley &, 2016. "Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    Full references (including those not matched with items on IDEAS)

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