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Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses
2024-10-09 38

Affiliations

  • Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Center of Molecular Medicine, Stockholm, Sweden.
  • Nykode Therapeutics, Oslo, Norway.
  • School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
  • Astrid Fagraeus Laboratory, Comparative Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Certara USA, Inc, Princeton, NJ, USA.
  • CureVac SE, Tübingen, Germany.
  • Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Department of Microbiology and Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
  • Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. karin.lore@ki.se.
  • Center of Molecular Medicine, Stockholm, Sweden. karin.lore@ki.se.

PMID:  37349310 PMCID:  PMC10287699 DOI: 10.1038/s41467-023-39421-5

Abstract

Background: Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, detailed investigations into the immune response are limited, and responses may be improved using novel vaccine platforms.

Methods: In this study, two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) were tested in non-human primates and compared to two doses of Rabipur. The mRNA vaccine showed a higher induction of RABV-G specific plasmablasts, T cells, and bone marrow plasma cells.

Results: The mRNA vaccine generated higher RABV-G binding and neutralizing antibody titers than Rabipur, which translated into improved cross-neutralization of related lyssavirus strains. The results suggest that this platform has potential for the development of a broadly protective vaccine against these viruses.

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