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| Status |
Public on Jul 01, 2024 |
| Title |
Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Andes virus (ANDV) is a rodent-borne zoonotic orthohantavirus endemic in South America that causes hantavirus pulmonary syndrome in humans, with up to a 40% case fatality rate. We developed ANDV mRNA vaccines based on the M segment of the viral genome that codes for glycoproteins Gn and Gc in a single open reading frame of glycoprotein precursor (GPC). We generated RNAs either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Mice immunized by either ANDV U-mRNA or m1Ψ-mRNA developed similar germinal center responses in lymph nodes. Single cell RNA and BCR sequencing of germinal center B cells from vaccinated mice demonstrated similar levels of activation, except an additional cluster of cells exhibiting strong interferon response that was present in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Furthermore, similar immunoglobulin class-switching and somatic hypermutations were observed for the two vaccines. Golden Syrian hamsters were immunized intramuscularly with 2 doses of the vaccines on days 0 and 21. The titers of Gn/Gc-binding antibodies were moderately greater for U-mRNA construct than for m1Ψ-mRNA construct, however, the titers of ANDV-neutralizing antibodies were equivalent. Vaccinated animals were challenged with a lethal dose of ANDV at 21 days after the boost, along with the naïve control group. All control animals succumbed to infection whereas all vaccinated animals survived without any detectable disease or viral load. The data demonstrate the development of effective vaccines against ANDV and the lack of a significant effect of m1Ψ mRNA modification on immunogenicity and protection in the hamster model.
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| Overall design |
Ten-week-old BALB/c mice, four per group, were immunized intramuscularly with one dose of 25 µg of either U-mRNA or m1Ψ-mRNA formulated with LNP. Twelve days after immunization animals were euthanized, and draining inguinal and popliteal lymph nodes harvested and pooled for each mouse for cell sorting. Germinal center B cells were sorted and sequenced to generate single cell 5' gene expression and V(D)J libraries.
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| Contributor(s) |
Kuzmin IV, Soto Acosta R, Wasdin P, Mire C, Engdahl TB, Moon WJ, Popov V, Crowe JE, Georgiev IS, Garcia-Blanco MA, Abbott RK, Bukreyev A |
| Citation(s) |
39080316 |
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| Submission date |
Aug 04, 2023 |
| Last update date |
Aug 23, 2024 |
| Contact name |
Ivelin Georgiev |
| Organization name |
Vanderbilt University Medical Center
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| Department |
Pathology, Microbiology, and Immunology
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| Street address |
11475 MRB IV 2213 Garland Ave
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| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| GSM7680764 |
Positive control, biol replicate 1, scRNA-seq |
| GSM7680765 |
Positive control, biol replicate 2, scRNA-seq |
| GSM7680766 |
Positive control, biol replicate 3, scRNA-seq |
| GSM7680767 |
Positive control, biol replicate 4, scRNA-seq |
| GSM7680768 |
Pseudouridine vaccine, biol replicate 1, scRNA-seq |
| GSM7680769 |
Pseudouridine vaccine, biol replicate 2, scRNA-seq |
| GSM7680770 |
Pseudouridine vaccine, biol replicate 3, scRNA-seq |
| GSM7680771 |
Pseudouridine vaccine, biol replicate 4, scRNA-seq |
| GSM7680772 |
Uridine vaccine, biol replicate 1, scRNA-seq |
| GSM7680773 |
Uridine vaccine biol replicate 2, scRNA-seq |
| GSM7680774 |
Uridine vaccine, biol replicate 3, scRNA-seq |
| GSM7680775 |
Uridine vaccine, biol replicate 4, scRNA-seq |
| GSM7680776 |
Negative control, biol replicate 1, scRNA-seq |
| GSM7680777 |
Negative control, biol replicate 2, scRNA-seq |
| GSM7680778 |
Negative control, biol replicate 3, scRNA-seq |
| GSM7680779 |
Negative control, biol replicate 4, scRNA-seq |
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| This SubSeries is part of SuperSeries: |
| GSE240064 |
Comparison of unmodified and modified mRNA platforms for Andes virus mRNA vaccine in rodent models |
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| Relations |
| BioProject |
PRJNA1002186 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240062_processed_concatenated_adata.h5ad.gz |
381.9 Mb |
(ftp)(http) |
H5AD |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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