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A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and tissue-resident T cell response in the lungs and protects hamsters against SARS-CoV-2

ABSTRACT: A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and tissue-resident T cell response in the lungs and protects hamsters against SARS-CoV-2

PROVIDER: PRJNA795672 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17499343.fastq.gz	Fastqsanger.gz
	SRR17499344.fastq.gz	Fastqsanger.gz
	SRR17499345.fastq.gz	Fastqsanger.gz
	SRR17499346.fastq.gz	Fastqsanger.gz
	SRR17499347.fastq.gz	Fastqsanger.gz

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A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and tissue-resident T cell response in the lungs and protects hamsters against SARS-CoV-2

Project description:Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust tissue-resident T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.

2022-05-04 | GSE193288 | GEO

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response (Hamster Lung RNA-seq Data)

Project description:The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-γ) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden. To investigate the immune response, pathological process caused by SARS-CoV-2 Beta variants infection in Golden Hamster lung. Golden hamsters were vaccinated with dNS1-RBD vaccine at day0 and day 14, and 2 months later the vccinated hamster were challenged with SARS-CoV-2 Beta varians together with control group hamster. Then the lung samples were collected at 0, 1, 3, 5 post infection to sequence for the RNA-seq data, then performed gene expression analysis using data obtained from RNA-seq.

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RNA-sequencing identifies the activation of IFN-dependent and IFN-independent pathways in the lungs of hamsters treated with NanoSTING

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Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response (Hamster AMs ATAC-seq Data)

Project description:The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-γ) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden. To investigate the trainned-immunity of alveolar macrophage generated by dNS1-RBD vaccine in Golden Hamster, we vaccinated Golden Hamster with dNS1-RBD/dNS1-Vector/PBS and collect the alveolar macrophage samples to sequence for the ATAC-seq data 2 months post vaccinated. Then performed the differential peak and igv track visualization with this dataset.

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A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2.

Project description:Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust memory T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.

| S-EPMC9038905 | biostudies-literature

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response

Project description:Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response

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