%0 Journal Article
%T Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine.
%A Kuzmin IV
%A Soto Acosta R
%A Pruitt L
%A Wasdin PT
%A Kedarinath K
%A Hernandez KR
%A Gonzales KA
%A Hill K
%A Weidner NG
%A Mire C
%A Engdahl TB
%A Moon WJ
%A Popov V
%A Crowe JE
%A Georgiev IS
%A Garcia-Blanco MA
%A Abbott RK
%A Bukreyev A
%J Nat Commun
%V 15
%N 1
%D 2024 Jul 30
%M 39080316
%F 17.694
%R 10.1038/s41467-024-50774-3
%X 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.