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Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses

Author

Listed:
  • Fredrika Hellgren

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine)

  • Alberto Cagigi

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine
    Nykode Therapeutics)

  • Rodrigo Arcoverde Cerveira

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine)

  • Sebastian Ols

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine)

  • Theresa Kern

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine)

  • Ang Lin

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine
    China Pharmaceutical University)

  • Bengt Eriksson

    (Karolinska Institutet)

  • Michael G. Dodds

    (Certara USA, Inc)

  • Edith Jasny

    (CureVac SE)

  • Kim Schwendt

    (CureVac SE)

  • Conrad Freuling

    (Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Thomas Müller

    (Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Martin Corcoran

    (Karolinska Institutet)

  • Gunilla B. Karlsson Hedestam

    (Karolinska Institutet)

  • Benjamin Petsch

    (CureVac SE)

  • Karin Loré

    (Karolinska Institutet and Karolinska University Hospital
    Center of Molecular Medicine)

Abstract

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

Suggested Citation

  • Fredrika Hellgren & Alberto Cagigi & Rodrigo Arcoverde Cerveira & Sebastian Ols & Theresa Kern & Ang Lin & Bengt Eriksson & Michael G. Dodds & Edith Jasny & Kim Schwendt & Conrad Freuling & Thomas Mül, 2023. "Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39421-5
    DOI: 10.1038/s41467-023-39421-5
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    References listed on IDEAS

    as
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    Cited by:

    1. Dan Fu & Wenming Wang & Yan Zhang & Fan Zhang & Pinyi Yang & Chun Yang & Yufei Tian & Renqi Yao & Jingwu Jian & Zixian Sun & Nan Zhang & Zhiyu Ni & Zihe Rao & Lei Zhao & Yu Guo, 2024. "Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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