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Transcriptional responses to oral live attenuated typhoid vaccines

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100665 | GEO | 2017/10/12

SECONDARY ACCESSION(S): PRJNA392453

REPOSITORIES: GEO

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Homo sapiens

Project description:Transcriptional responses to oral live attenuated typhoid vaccines

| PRJNA392453 | ENA

Affect of antiviral ribavirin on YFV WT and vaccine strains.

Project description:Live-attenuated viral vaccines have been successfully used to combat infectious disease for decades but due to their empirical derivation, little is known about their mechanisms of attenuation. This lack of understanding makes the development of next generation live attenuated vaccines difficult. The success of the 17D vaccine and availability of the parent virus, Asibi, makes it an excellent model to understand the molecular basis of attenuation of a live attenuated vaccine and the effects of viral diversity on vaccine function. Due to the differences in genetic diversity between WT Asibi virus and its 17D vaccine derivative, we investigated the changes in genetic diversity of 17D and Asibi viruses following treatment with ribavirin.

2020-01-01 | E-MTAB-8504 | biostudies-arrayexpress

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

Project description:Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) from 30 subjects collected at day 0, day 1 and day 3 post yellow fever (YF) vaccination. Each patient sample is performed in duplicate to reduce the chance of error. Briefly, the project investigates how cross-reactive JE antibodies that are generated from prior vaccination can influence YF live-attenuated vaccine (LAV). The groups are hence segregated based on the YF antibody titers after 1 month vaccination. Group 4 refers to the control group where individuals received only the YF LAV. Enhancing group refers to the treatment group (given JE followed by YF vaccine), where individuals had YF antibody titers higher than 99% confidence interval of the YF antibody titers of the control group. Non-enhancing group, on the other hand, refers to the treatment group where individuals had YF antibody titers within or lower 99% confidence interval of the control group. Our present study provides evidence that enhancing levels of cross-reactive antibodies from prior Japanese encephalitis (JE) vaccination can improve subsequent YF immunogenicity. These microarray results indicate the genes and gene signatures that are associated with the differences in YF immunogenicity.

2017-09-05 | E-MTAB-4669 | biostudies-arrayexpress

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Project description:Brucellosis is a serious zoonotic disease caused by the genus Brucella, a group of Gram-negative and facultative intracellular bacteria. At present, although live attenuated vaccine such as Rev.1, S19 and RB51 have been widely used for bovine brucellosis, these vaccines have some drawbacks, and safe and effective alternatives have been demanded. Previously, our group showed that several Brucella proteins malate dehydrogenase (rMDH) are effective in eliciting IgG responses in murine model following intraperitoneal injection. The Brucella infections are usually transmitted through mucosal membrane via oral or aerosol exposure. Therefore, induction of mucosal immunity is promising contribute in development of vaccine. In the study, rMDH was loaded with chitosan nanoparticles (CNs) which is mucoadhesive, biocompatible, nontoxic, and immune-enhancing adjuvant to induce both systemic and mucosal immunity. Then, in order to evaluate immunogenicity of the antigen in BALB/C mouse, total RNA from nasal-associated lymphoid tissues at 1 h, 6 h, 12 h after intranasal immunization was analyzed using RNA-seq.

2019-01-29 | GSE125765 | GEO

NK cell immune responses differ after prime and boost vaccination

Project description:A better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. Here, we studied the diversity and dynamics of the NK cell compartment after prime-boost immunization with the modified vaccinia virus Ankara using cynomolgus macaques as a model. Mass cytometry was used to deeply characterize blood NK cells. The NK cell subphenotype composition was modified by the prime. Certain phenotypic changes induced by the prime were maintained over time and, as a result, the NK cell composition prior to boost differed from that before prime. The key phenotypic signature that distinguished NK cells responding to the boost from those responding to the prime included stronger expression of several cytotoxic, homing, and adhesion molecules, suggesting that NK cells at recall were functionally distinct. Our data reveal potential priming or imprinting of NK cells after the first vaccine injection. This study provides novel insights into prime-boost vaccination protocols that could be used to optimize future vaccines.

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2020-06-30 | GSE149809 | GEO

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2022-12-13 | GSE217770 | GEO

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Project description:Typhoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Bulk RNA-sequencing (RNA-seq) data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial involving two vaccines against typhoid fever, a plain polysaccharide vaccine, ViPS and a glycoconjugate vaccine, ViTCV. The participants were then challenged with S. Typhi in a controlled human infection model (CHIM).

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A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S)

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2023-10-19 | GSE230494 | GEO

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