Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model.

ABSTRACT: Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low-middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.

SUBMITTER: Pilla G

PROVIDER: S-EPMC8468197 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Evaluation of a Live Attenuated Human Metapneumovirus Vaccine in Adults and Children.

Project description:We conducted a phase I clinical trial of an experimental live attenuated recombinant human metapneumovirus (HMPV) vaccine (rHMPV-Pa) sequentially in adults, HMPV-seropositive children, and HMPV-seronegative children, the target population for vaccination. rHMPV-Pa was appropriately restricted in replication in adults and HMPV-seropositive children but was overattenuated for HMPV-seronegative children.

| S-EPMC6075531 | biostudies-literature

Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates.

Project description:Human respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5' to 3') a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

| S-EPMC8379332 | biostudies-literature

Evaluation of efficacy and effectiveness of live attenuated zoster vaccine.

Project description:Herpes zoster (HZ) is a viral disease characterized by a dermatologic and neurologic involvement caused by the reactivation of the latent varicella zoster virus (VZV) acquired during primary infection (varicella). HZ incidence increases with age and is related to waning specific cell-mediated immunity (CMI). The most frequent complication of HZ is post-herpetic neuralgia (PHN) characterized by chronic pain lasting at least 30 days, with impact on patients' quality of life. Available treatments are quite unsatisfactory in reducing pain and length of the disease. The evaluation of the epidemiology, the debilitating complications (PHN), the suboptimal available treatments and the costs related to the diagnosis and clinical/therapeutic management of HZ patients have been the rationale for the search of an adequate preventive measure against this disease. The target of this intervention is to reduce the frequency and severity of HZ and related complications by stimulating CMI. Prevention has recently become possible with the live attenuated vaccine Oka/Merck, with an antigen content at least 10-fold higher than the antigen content of pediatric varicella vaccines. Clinical studies show a good level of efficacy and effectiveness, particularly against the burden of illness and PHN in all age classes. Accordingly to the summary of the characteristics of the product the zoster vaccine is indicated for the prevention of HZ and PHN in individuals 50 years of age or older and is effective and safe in subjects with a positive history of HZ.

| S-EPMC4718315 | biostudies-other

Evaluation of a Live-Attenuated Human Parainfluenza Type 1 Vaccine in Adults and Children.

Project description:We conducted a phase I clinical trial (clinicaltrials.gov identifier, NCT00641017) of the experimental live-attenuated human parainfluenza virus type 1 (HPIV-1) vaccine rHPIV-1/84/del 170/942A sequentially in 3 groups: adults, HPIV-1-seropositive children, and HPIV-1-seronegative children, the target population for vaccination. rHPIV-1/84/del 170/942A was appropriately restricted in replication in adults and HPIV-1-seropositive children but was overattenuated (ie, insufficiently infectious and immunogenic) for HPIV-1-seronegative children.

| S-EPMC4681387 | biostudies-literature

Development and Evaluation of a Live Attenuated Egg-Based Camelpox Vaccine.

Project description:Camelpox is an infectious viral disease of camels reported in all the camel-breeding areas of Africa, north of the equator, the Middle East and Asia. It causes huge economic loss to the camel industry. We developed a live camelpox virus vaccine candidate using an attenuated strain and evaluated its safety, immunogenicity and protective efficacy in camels. The attenuated virus strain was generated from the camelpox wild-type strain M-96 by 40 consecutive passages on the chorioallantoic membrane of 11-day-old embryonated chicken eggs, henceforth called KM-40 strain. Reversion to virulence of the KM-40 strain was evaluated in camels by three serial passages, confirmed its inability to revert to virulence and its overdose administration was also found safe. Studies of immunogenicity and protective efficacy of the candidate vaccine KM-40 strain in camels was carried out using the dose of 5 x 104.0 EID50. Our data showed complete protection against the challenge infection using the virulent wild-type camelpox virus strain M-96 (dose of 105.0 EID50) which was evaluated at 1, 3, 6 and 12 months post vaccination. In summary, our candidate live attenuated egg-based camelpox vaccine strain KM-40 was found safe, protective, and thus has the potential to use safely in field conditions.

| S-EPMC8415447 | biostudies-literature

Safety and Transcriptome Analysis of Brucella Live Attenuated Vaccine Strain S2 on Cynomolgus Monkeys

Project description:Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine.

2021-03-04 | GSE165283 | GEO

Complete Genome Sequence of the Live Attenuated Vaccine Strain Brucella melitensis Rev.1.

Project description:Live attenuated vaccines are essential elements in control programs for the prevention of brucellosis. Here, we report the whole-genome sequence of the original Elberg Brucella melitensis Rev.1 vaccine strain, passage 101 (1970). Commercial lines of the original strain have been successfully used in small ruminants worldwide.

| S-EPMC5864954 | biostudies-literature

A live attenuated strain of Yersinia pestis KIM as a vaccine against plague.

Project description:Yersinia pestis, the causative agent of plague, is a potential weapon of bioterrorism. Y. pestis evades the innate immune system by synthesizing tetra-acylated lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity at 37°C, whereas hexa-acylated lipid A, a potent TLR4 agonist, is made at lower temperatures. Synthesis of Escherichia coli LpxL, which transfers the secondary laurate chain to the 2'-position of lipid A, in Y. pestis results in production of hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Previously, we described a Y. pestis vaccine strain in which crp expression is under the control of the arabinose-regulated araC P(BAD) promoter, resulting in a 4-5 log reduction in virulence. To reduce the virulence of the crp promoter mutant further, we introduced E. coli lpxL into the Y. pestis chromosome. The χ10030(pCD1Ap) (ΔlpxP32::P(lpxL)lpxL ΔP(crp21)::TT araC P(BAD)crp) construct likewise produced hexa-acylated lipid A at 37°C and was significantly more attenuated than strains harboring each individual mutation. The LD(50) of the mutant in mice, when administered subcutaneously or intranasally was >10(7)-times and >10(4)-times greater than wild type, respectively. Mice immunized subcutaneously with a single dose of the mutant were completely protected against a subcutaneous challenge of 3.6×10(7) wild-type Y. pestis and significantly protected (80% survival) against a pulmonary challenge of 1.2×10(4) live cells. Intranasal immunization also provided significant protection against challenges by both routes. This mutant is an immunogenic, highly attenuated live Y. pestis construct that merits further development as a vaccine candidate.

| S-EPMC3073832 | biostudies-literature

Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid.

Project description:The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with virulence genes, it exhibits dormant pathogenicity and can cause fowl typhoid in young chicks and stressed or immunocompromised brown egg-laying hens. To tackle these issues, we knocked out the rfaJ gene of SG9R (named Safe-9R) to eliminate the reversion risk and generated detoxified strains of Safe-9R by knocking out lpxL, lpxM, pagP, and phoP/phoQ genes to attenuate the virulence. Among the knockout strains, live ΔlpxL- (Dtx-9RL) and ΔlpxM-9R (Dtx-9RM) strains induced remarkably less expression of inflammatory cytokines in chicken macrophage cells, and oil emulsion (OE) Dtx-9RL did not cause body weight loss in chicks. Live Dtx-9RM exhibited efficacy against field strain challenge in one week without any bacterial re-isolation, while the un-detoxified strains showed the development of severe liver lesions and re-isolation of challenged strains. Thus, SG9R was optimally detoxified by knockout of lpxL and lpxM, and Dtx-9RL and Dtx-9RM might be applicable as OE and live vaccines, respectively, to prevent fowl typhoid irrespective of the age of chickens.

| S-EPMC7913755 | biostudies-literature

Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer ImmunotherapyRepurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data