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

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. Engdahl, Woohyun J. Moon, Vsevolod Popov, James E. Crowe, Ivelin S. Georgiev, Mariano A. Garcia-Blanco, Robert K. Abbott () and Alexander Bukreyev ()
Additional contact information
Ivan V. Kuzmin: University of Texas Medical Branch
Ruben Soto Acosta: University of Texas Medical Branch
Layne Pruitt: University of Texas Medical Branch
Perry T. Wasdin: Vanderbilt Vaccine Center
Kritika Kedarinath: University of Texas Medical Branch
Keziah R. Hernandez: University of Texas Medical Branch
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
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
Robert K. Abbott: University of Texas Medical Branch
Alexander Bukreyev: University of Texas Medical Branch

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50774-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50774-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50774-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().