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Transcriptional profiles in human milk and whole blood after live attenuated and inactivated influenza vaccination

ABSTRACT: Transcriptional profiles in human milk and whole blood after live attenuated and inactivated influenza vaccination

PROVIDER: PRJNA802214 | ENA |

REPOSITORIES: ENA

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Transcriptional profiles in human milk and whole blood after live attenuated and inactivated influenza vaccination

Project description:Breastfeeding protects against mucosal infections in infants. The underlying mechanisms through which immunity develops in human milk following maternal infection with mucosal pathogens are not well understood. We simulate mucosal influenza infection through live attenuated influenza vaccination (LAIV) and compared milk and blood immune responses to inactivated influenza vaccination (IIV). Transcriptomic analysis was performed on RNA extracted from human milk and whole blood. Differentially expressed genes (DEGs) and gene set enrichment analysis (GSEA) on days 1 and 7 post-vaccination were compared to pre-vaccination.

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Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children.

Project description:The reasons for differences in vaccine effectiveness between live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are not clea Blood samples were obtained before vaccination and at days 7 and 21 postvaccination with 2015-2016 quadrivalent IIV or LAIV. Serologic response to the vaccine was measured by hemagglutination inhibition assay. Targeted RNA sequencing and serum cytokine analysis were performed. Paired analyses were used to determine gene expression and were compared between IIV and LAIV recipients.

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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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Live Attenuated Tetravalent Dengue Vaccination in Non-Human Primates

Project description:We measured genome-wide transcript abundance patterns in 246 whole blood samples collected from 35 cynomolgus macaques before and after vaccination with a live attenuated tetravalent dengue vaccine (TDV) or PBS (placebo). Animal work was conducted at the Charmany Instructional Facility of the School of Veterinary Medicine, University of Wisconsin-Madison, and all animal procedures were approved by the University of Wisconsin-Madison's Animal Care and Use Committee. Thirty-five adult male, DENV-seronegative cynomolgus macaques from Vietnam were placed in quarantine for 30 days prior to the start of the study. Five groups of animals (n=6 animals per group) received TDV either subcutaneously (SC) in 0.5 mL inocula or intradermally (ID) in 0.1 mL inocula using a needle-free injector (PharmaJet' device) or needle and syringe (N&S). Animals received two doses (same route) of TDV either on the same day (Day 0) or sixty days apart. One group (n=5) received PBS by ID route and needle-free injector. On day 90 after primary vaccination, 3 animals from each group were challenged with 105 PFU wt DENV-2 (New Guinea C strain) or 105 PFU wt DENV-4 (Dominica/81 strain) by SC route using N&S. Whole blood samples were collected for transcriptional profiling from all animals on days -11, -2, 1, 3, 5, and 7 before and after immunization, and for placebo animals on days 88, 91, 93, 95, and 97 before and after wt DENV challenge. Blood samples were drawn into PAXgene Blood RNA tubes and stored at -80'C prior to RNA extraction and processing.

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

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