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Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells

ABSTRACT: Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells

PROVIDER: PRJNA325484 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3591010_1.fastq.gz	Fastqsanger.gz
	SRR3591010_2.fastq.gz	Fastqsanger.gz
	SRR3591011_1.fastq.gz	Fastqsanger.gz
	SRR3591011_2.fastq.gz	Fastqsanger.gz
	SRR3591012_1.fastq.gz	Fastqsanger.gz

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Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells [Microarray Expression]

Project description:The host innate immune response to influenza virus is a key determinant of pathogenic outcomes and long-term protective responses against subsequent exposures. Comparison of the transcriptional profiles obtained 24 and 36 hrs post-infection showed that the magnitude of gene expression was greater in LAIV infected cells relative to that observed in WT infected cells. Functional enrichment analysis revealed that the antiviral and inflammatory responses was largely driven by type III IFN induction in both WT and LAIV infected cells. However, the enrichment of biological pathways involved in the recruitment of mononuclear leukocytes, antigen presenting cells, and T lymphocytes was uniquely observed in LAIV infected cells. These findings indicate that cell-intrinsic type III IFN-mediated innate immune responses in the nasal epithelium are not only crucial for viral clearance and attenuation, but may also play an important role in the immunogenicity of live-attenuated vaccines

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Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells [RNA-Seq]

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Transcriptional responses to oral live attenuated typhoid vaccines

Project description:Enteric fever is a major public health problem and causes numerous deaths annually. Ty21a is the only efficacious oral, live attenuated typhoid vaccine currently licensed for use, however, its mechanism of protection is poorly understood. To address this knowledge gap, we interrogated transcriptional profiles following vaccination with Ty21a and an immunogenic experimental oral live attenuated vaccine, M01ZH09, and related these findings to immunogenicity, and incubation period and disease severity following challenge with Salmonella Typhi four weeks after vaccination. Despite originating from the same parent strain (Ty2), we detected marked differences in the gene expression between both vaccines. Analysis of the transcriptome 7 days after M01ZH09 vaccination implicated transcriptional patterns associated with the cell cycle correlated significantly with humoral immunogenicity 28 days after vaccination. In contrast, significantly induced T and NK cell responses were associated with Ty21a vaccination, and integrative analysis indicated signatures reflecting amino acid metabolism with delayed onset of disease. Stimulation of PBMCs collected from participants prior to and following vaccination with the two vaccine strains in vitro confirmed the superior capacity of Ty21a to induce NK cells, validating gene expression results. These data provide insight into the effects of oral live attenuated typhoid vaccines on the human molecular immune response and underline the involvement of T cell response signatures with protection following challenge.

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Project description:Purpose: Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. Methods: In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Results: Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. Conclusions: These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.

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Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity

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Network Analysis Reveals Age- and Virus-Specific Circuits in Nasal Epithelial Cells of Extremely Premature Infants

Project description:Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Despite posing substantial health risks, airway immune responses in early life remain largely unexplored. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular networks for influenza A and respiratory syncytial virus, emphasizing highly relevant virus-specific pathways. This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers novel insights that should enable a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.

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