ETEC wild types and attenuated vaccine strains
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REPOSITORIES: ENA
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Project description:Enterotoxigenic Escherichia coli (ETEC) infections are a common cause of diarrheal illness in low- and middle-income countries. The live-attenuated ACE527 vaccine, adjuvanted with double mutant LT (dmLT), affords clear but partial protection against ETEC challenge inhuman volunteers. Comparatively, initial wild-type ETEC challenge completely protects against severe diarrhea on homologous re-challenge...To investigate molecular determinants of protection, vaccine antigen content was compared to wild-type ETEC, and proteome microarrays were used to assess immune responses following vaccination and ETEC challenge... Although molecular interrogation of the vaccine confirmed expression of targeted canonical antigens, relative to wild-type ETEC, vaccine strains were deficient in production of flagellar antigens, immotile, and lacked production of the EtpA adhesin. Similarly, vaccination ± dmLT elicited responses to targeted canonical antigens, but relative to wild-type challenge, vaccine responses to some potentially protective non-canonical antigens including EtpA were diminished or absent...These studies highlight important differences in vaccine and wild-type ETEC antigen content and call attention to distinct immunologic signatures that could inform investigation of correlates of protection, and guide vaccine antigen selection for these pathogens of global importance.
2019-07-25 | GSE134792 | GEO
Project description:Enterotoxigenic E. coli (ETEC) is a major cause of moderate to severe diarrhoea in low-middle income countries (LMICs) and affects mostly children and travelers to endemic regions. ETEC are highly diverse pathovar with over 25 colonisation factors (fimbriae) described. The development of a broadly protective vaccine to cover most of the ETEC variants is critical for disease control. This study evaluated whether vaccination with ETVAX®; the most clinically advanced ETEC vaccine candidate results in IgG responses that cross-react with other ETEC antigens/ colonisation factors not overexpressed in the vaccine. A proteome microarray was used to assess IgG responses before and after vaccination to gain insight in the antigenic composition of ETEC that children in Zambia are exposed to and to see whether ETVAX® provides a level of cross-protection against antigens not expressed in the vaccine. The study shows that ETVAX® containing CFA/1, elicits antibodies that cross-react with other class 5 fimbriae and has the potential to offer broad protection. We also see that other antigens apart from classical antigens are immunodominant and possibly play a role in ETEC pathogenesis and may need to be investigated for their role in protection
2023-05-31 | GSE220814 | GEO
Project description:PFGRC has developed a cost effective alternative to complete genome sequencing in order to study the genetic differences between closely related species and/or strains. The comparative genomics approach combines Gene Discovery (GD) and Comparative Genomic Hybridization (CGH) techniques, resulting in the design and production of species microarrays that represent the diversity of a species beyond just the sequenced reference strain(s) used in the initial microarray design. These species arrays may then be used to interrogate hundreds of closely related strains in order to further unravel their evolutionary relationships. Infectious diarrhea is a leading worldwide cause of infant mortality and secondary malnutrition. Enterotoxigenic E. coli (ETEC) is a principal etiology of travelers?diarrhea and a major endemic health threat, especially among children in developing nations where it is estimated to cause hundreds of thousands of deaths each year. Vaccine development for ETEC has been significantly hampered by the remarkable genetic plasticity of E. coli, a comparatively modest understanding of the basic pathogenesis of these organisms, and an uncertainty regarding the degree to which any given antigenic target might be conserved. While experimental and epidemiologic data suggest that a broadly protective vaccine can be achieved, this will most effectively be accomplished in a research environment that fosters sharing of vital resources and open, collaborative interactions among multiple investigators. The proposed project is aimed at providing critical leverage to ongoing international investigative efforts pertaining to ETEC pathogenesis and vaccinology. The flow of genetic information within this group motivated us to identify novel genes for the purpose of creating a species DNA microarray to better understand the ancestral relationships among its members. Based on preliminary MLST genotyping, 11 diverse ETEC strains were selected for sequencing. Sequence information obtained from this project, and from other publicly available sources, led to the development of a comprehensive species microarray for ETEC group members. The availability of the ETEC species DNA microarray has allowed us to carry out a collaborative CGH genotyping project to validate this microarray as well as understand the phylogenomic relationships among members of ETEC group.
2010-12-07 | GSE25601 | GEO
Project description:Complete data set for "Molecular and immunological interrogation of a live-attenuated enterotoxigenic Escherichia coli vaccine highlights features unique to wild type infection"
2019-07-23 | MSV000084121 | MassIVE
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
Project description:Impact of live attenuated F. tularensis vaccine (DVC-LVS) on PBMC poly(A)-RNA expresssion in 10 subjects over time (Days 1, 2 ,7, and 14 post-vaccination) relative to pre-vaccination (Day 0).
2020-06-30 | GSE149809 | GEO
Project description:ETEC is an important human pathogen. Although the mechanism of diarrhea is known in ETEC, the regulatory networks are less understood. This study was conducted to understand the global expression of ETEC isolate E24377A under different growth and environemental conditions. ETEC isolate E24377A was grown in the presence of several chemical signals, including bile salts, glucose, and pre-conditioned media (PCM) from other enteric pathogens. E24377A was also grown to different densities, to see if a quorum sensing mechanism was in place The isolate was grown in different types of media, with different ammendments, and at different growth densities. The overall goal was to determine how expression gene expression changes in the presence of chemical signals; a special emphasis was placed on the expression of known and suspected virulence and colonization factors
2012-03-01 | E-GEOD-31804 | biostudies-arrayexpress
Project description:In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulate a potent cytotoxic T cells immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC).
2022-10-27 | PXD031295 | Pride
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