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Henipavirus nipahense strain:Bangladesh

ABSTRACT: Efficacy of the 4-Florouridine nucleoside analog against Nipah virus in the Syrian hamster model

PROVIDER: PRJNA1214874 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32191900_1.fastq.gz	Fastqsanger.gz
	SRR32191900_2.fastq.gz	Fastqsanger.gz
	SRR32191901_1.fastq.gz	Fastqsanger.gz
	SRR32191901_2.fastq.gz	Fastqsanger.gz
	SRR32191902_1.fastq.gz	Fastqsanger.gz

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Project description:1. The experiment was performed to assess if the newly discovered Syrian hamster specific anti-PD-L1 antibody could induce a biologically relevant change in transcriptome profile in the tumours. This would confirm that the antibody has functional properties. In the larger picture, the Syrian Hamster model is favored over the mouse model for the development of vaccines and testing of oncolytic viruses/immunotherapies. This is because the model is semi permissive to virus replication compared to the mouse model. We can therefore more reliably assess the efficacy of oncolytic virotherapies, mainly oncolysis and promoter specific transgene expression. Moreover, we wanted to test potential improvements to treatment outcomes when combining oncolytic virotherapy and immune checkpoint blockade. However, there are not many commercially available research tools specific to the Syrian Hamster. This is why we developed an in vivo compatible immune checkpoint inhibitor so that we could assess the combination therapy in the Syrian hamster model. Lastly, we also wanted to validate if we could assess the efficacy of the immunotherapies using biopsies from hamsters to remove unnecessary use of animals. 2. To do this, we engrafted one PDAC tumours on the right flank of Syrian hamsters using 5 x10E+6 HapT1 cells grown in culture. When tumours reached 4-5mm in diameter, the hamsters were injected intraperitoneally with either 300ug of IgG2a control or anti-PD-L1 (clone;11B12-1). Hamsters were treated 8 times and a tumour biopsy was taken one day before the last treatment. The biopsy was immediately stored in RNA-later until extraction with RNA mini kit (Qiagen).

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Project description:Nipah virus (NiV) is an emerging paramyxovirus which causes severe respiratory illness and deathly encephalitis in humans.Improving the ability of vaccines to induce strong, cellular, and humoral immune responses, remains the challenge to respond to Nipah and future Henipavirus infections rapidly and efficiently. A CD40.NiV vaccine has been engineered by fusing to the anti-CD40 monoclonal Ab the ectodomain of the Nipah G protein (Bangladesh strain) and immunogenic and conserved NiV F and N peptides. In mice, CD40.NiV promotes poly-antigenic T cell responses and significantly improves anti-NiV G IgG responses compared to the non-targeted NiV G immunogenic protein, in terms of avidity and neutralization potency. Immunogenicity was confirmed in the AGM (African Green Monkey) model, with induction of cross-neutralizing sera against circulating NiV strains and Hendra virus (HeV). Challenge experiment using NiV-B strain demonstrated the high protective efficacy of the vaccine with 100% survival in vaccinated group as compared to 100% lethality in controls. Surviving animals did not exhibit NiV viral replication in the blood, organs and swabs suggesting a sterilizing immunity conferred by the CD40.NiV vaccine. Taken together, results obtained with CD40.NiV vaccine are highly promising in terms of breadth and viral efficacy against NiV.

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