Related Experiment Video
Updated: Jun 18, 2025
Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy
Published on: November 1, 2011
Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
Ivan V Kuzmin1,2, Ruben Soto Acosta1,2, Layne Pruitt1
1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
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.
Insights
Researchers developed an Andes virus (ANDV) mRNA vaccine. Both regular uridine (U-mRNA) and N1-methylpseudouridine (m1Ψ-mRNA) vaccines protected rodents against lethal ANDV challenge, showing similar efficacy.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Andes virus (ANDV) is a rodent-borne hantavirus causing severe human disease.
- Effective vaccines are crucial for preventing ANDV infection and its associated morbidity and mortality.
Purpose of the Study:
- To develop and evaluate an mRNA vaccine candidate targeting the M segment of the Andes virus.
- To compare the immunogenicity and protective efficacy of two mRNA formulations: regular uridine (U-mRNA) and N1-methylpseudouridine (m1Ψ-mRNA).
Main Methods:
- Development of ANDV mRNA vaccines based on the M segment, utilizing either U or m1Ψ modifications.
- Immunization of female mice and Syrian hamsters with U-mRNA and m1Ψ-mRNA vaccines.
- Assessment of germinal center responses, B cell activation, immunoglobulin class-switching, and somatic hypermutations.
- Measurement of glycoprotein-binding and neutralizing antibody titers.
- Challenge studies with a lethal dose of ANDV in vaccinated and control animals.
Main Results:
- Both U-mRNA and m1Ψ-mRNA vaccines elicited immune responses in mice, with m1Ψ-mRNA showing slightly greater germinal center responses.
- Single-cell sequencing revealed similar B cell activation, with an interferon response cluster observed in U-mRNA vaccinated mice.
- Hamster immunization showed higher glycoprotein-binding antibodies for U-mRNA but similar ANDV-neutralizing antibody titers for both vaccine types.
- All vaccinated animals survived a lethal ANDV challenge, while control animals succumbed to infection.
Conclusions:
- The developed mRNA vaccine provides protection against lethal Andes virus infection in rodent models.
- The N1-methylpseudouridine modification did not substantially alter the overall immunogenicity or protective efficacy of the ANDV mRNA vaccine in this study.
- These findings support the potential of mRNA technology for developing vaccines against hantaviruses like ANDV.
