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Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine

Author

Listed:
  • Ivan V. Kuzmin

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Ruben Soto Acosta

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Layne Pruitt

    (University of Texas Medical Branch)

  • Perry T. Wasdin

    (Vanderbilt Vaccine Center)

  • Kritika Kedarinath

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Keziah R. Hernandez

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Kristyn A. Gonzales

    (University of Texas Medical Branch)

  • Kharighan Hill

    (University of Texas Medical Branch)

  • Nicole G. Weidner

    (University of Texas Medical Branch)

  • Chad Mire

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Taylor B. Engdahl

    (Vanderbilt Vaccine Center)

  • Woohyun J. Moon

    (Acuitas Therapeutics)

  • Vsevolod Popov

    (University of Texas Medical Branch)

  • James E. Crowe

    (Vanderbilt Vaccine Center)

  • Ivelin S. Georgiev

    (Vanderbilt Vaccine Center)

  • Mariano A. Garcia-Blanco

    (University of Texas Medical Branch
    University of Virginia)

  • Robert K. Abbott

    (University of Texas Medical Branch)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

Abstract

The rodent-borne Andes virus (ANDV) causes a severe disease in humans. We developed an ANDV mRNA vaccine based on the M segment of the viral genome, either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Female mice immunized by m1Ψ-mRNA developed slightly greater germinal center (GC) responses than U-mRNA-immunized mice. Single cell RNA and BCR sequencing of the GC B cells revealed similar levels of activation, except an additional cluster of cells exhibiting interferon response in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Similar immunoglobulin class-switching and somatic hypermutations were observed in response to the vaccines. Female Syrian hamsters were immunized via a prime–boost regimen with two doses of each vaccine. The titers of glycoprotein-binding antibodies were greater for U-mRNA construct than for m1Ψ-mRNA construct; however, the titers of ANDV-neutralizing antibodies were similar. Vaccinated animals were challenged with a lethal dose of ANDV, along with a naïve control group. All control animals and two animals vaccinated with a lower dose of m1Ψ-mRNA succumbed to infection whereas other vaccinated animals survived without evidence of virus replication. The data demonstrate the development of a protective vaccine against ANDV and the lack of a substantial effect of m1Ψ modification on immunogenicity and protection in rodents.

Suggested Citation

  • Ivan V. Kuzmin & Ruben Soto Acosta & Layne Pruitt & Perry T. Wasdin & Kritika Kedarinath & Keziah R. Hernandez & Kristyn A. Gonzales & Kharighan Hill & Nicole G. Weidner & Chad Mire & Taylor B. Engdah, 2024. "Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50774-3
    DOI: 10.1038/s41467-024-50774-3
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