Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms [scRNA-seq]
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PROVIDER: PRJNA1002186 | ENA |
REPOSITORIES: ENA
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Project description:Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms [VDJ-seq]
| PRJNA1002184 | ENA
Project description:Comparison of unmodified and modified mRNA platforms for Andes virus mRNA vaccine in rodent models Kuzmin IV, Soto-Acosta R, Pruitt L, Wasdin PT, Kedarinath K, Hernandez KR, Gonzales KA, Hill K, Weidner NG, Mire C, Engdahl TB, Moon WJ, Popov V, Crowe JE, Georgiev IS, Garcia-Blanco MA, Abbott RK, Bukreyev A. This SuperSeries is composed of the SubSeries listed below.
2024-07-01 | GSE240064 | GEO
Project description: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.
2024-07-01 | GSE240063 | GEO
Project description: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.
2024-07-01 | GSE240062 | GEO
Project description:Comparison of unmodified and modified mRNA platforms for Andes virus mRNA vaccine in rodent models
| PRJNA1002143 | ENA
Project description:mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.
2024-09-04 | GSE260817 | GEO
Project description:The COVID mRNA vaccines utilize the modified nucleobase N1-methylpseudouridine, in place of canonical uridine, to improve immunogenicity and protein yield. However, relatively few studies have investigated the effect of modified nucleobases on the fidelity of protein translation. Given the interest in the COVID mRNA vaccines, we sought to investigate how N1-methylpseudouridine (and the related modification pseudouridine) is read by ribosomes.
2022-08-18 | PXD029291 | Pride
Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquí population living in the Calchaquí Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude.
2014-04-05 | GSE56518 | GEO
Project description:Profiling of mRNA abundances with high-throughput platforms such as microarrays and RNA-Seq has become an important tool in both basic and biomedical research. However these platforms remain prone to systematic errors, and have challenges in clinical and industrial application. As a result it is standard practice to validate a subset of key results using alternate technologies. Similarly, clinical and industrial applications typically involve transitions from high-throughput discovery platform to medium-throughput validation ones. These medium-throughput validation platforms have high technical reproducibility and reduced sample input needs, and low sensitivity to sample-quality (e.g. for processing FFPE specimens). Unfortunately, while medium-throughput platforms have proliferated, there are no comprehensive comparisons of them. Here we present ABI's OpenArray and qPCR systems.
2012-10-18 | GSE41388 | GEO
Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquà population living in the Calchaquà Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude. DNA from 24 saliva samples of CalchaquÃes living at 2300 m in Cachi in the Province of Salta in Argentina was genotyped.
2014-04-05 | E-GEOD-56518 | biostudies-arrayexpress