Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Novel Chimeric Antigen as a Vaccine Candidate against Leishmania major: In silico Analysis.

ABSTRACT:

Background

Leishmania is a mandatory intracellular pathogen and causing neglected disease. Hence, protection against leishmaniasis by a development vaccine is an important subject. This study aimed to design a poly-epitope vaccine for cutaneous leishmaniasis.

Methods

The present study was conducted in the Parasitology Department of Tarbiat Modares University, Tehran, Iran during 2017-2019. Several bioinformatics methods at online servers were used for prediction of different aspects of poly-epitope, including, physico-chemical attributes, allergenicity, antigenicity, secondary and tertiary structures, B-cell, T-cell and MHC (I, II) potential epitopes of LACK, LEIF, GP63 and SMT antigens of L. major.

Results

After designing the construct (GLSL), the outputs of PTM sites demonstrated that the poly-epitope had 57 potential sites for phosphorylation. Furthermore, the secondary of GLSL structure includes 59.42%, 20.94% and 19.63% for random coil, extended strand and alpha-helix, respectively. The GLSL is an immunogenic protein with an acceptable antigenicity (0.8410) and non-allergen. Afterward, 20 potential epitopes of LACK, LEIF, GP63 and SMT antigens were linked by a flexible linker (SAPGTP), then was synthesized, and sub-cloned in pLEXY- neo2. The results were confirmed the expression of 38.7 kDa poly-epitope in secretory and cytosolic sites, separately.

Conclusion

A good expression in the L. tarentulae and confirmation of the GLSL poly-epitope could be a basis for developing a vaccine candidate against leishmaniasis that should be confirmed via experimental tests in BALB/c mice.

SUBMITTER: Ahmadpour NB

PROVIDER: S-EPMC8418661 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

<i>In silico</i> analysis and expression of a new chimeric antigen as a vaccine candidate against cutaneous leishmaniasis.

Project description:ObjectivesSince leishmaniasis is one of the health problems in many countries, the development of preventive vaccines against it is a top priority. Peptide vaccines may be a new way to fight the Leishmania infection. In this study, a silicon method was used to predict and analyze B and T cells to produce a vaccine against cutaneous leishmaniasis.Materials and methodsImmunodominant epitope of Leishmania were selected from four TSA, LPG3, GP63, and Lmsti1 antigens and linked together using a flexible linker (SAPGTP). The antigenic and allergenic features, 2D and 3D structures, and physicochemical features of a chimeric protein were predicted. Finally, through bioinformatics methods, the mRNA structure was predicted and was produced chemically and cloned into the pLEXY-neo2 vector.ResultsResults indicated, polytope had no allergenic properties, but its antigenicity was estimated to be 0.92%. The amino acids numbers, molecular weight as well as negative and positive charge residuals were estimated 390, ~41KDa, 41, and 30, respectively. The results showed that the designed polytope has 50 post-translationally modified sites. Also, the secondary structure of the protein is composed of 25.38% alpha-helix, 12.31% extended strand, and 62.31% random coil. The results of SDS-PAGE and Western blotting revealed the recombinant protein with ~ 41 kDa. The results of Ramachandran plot showed that 96%, 2.7%, and 1.3% of amino acid residues were located in the preferred, permitted, and outlier areas, respectively.ConclusionIt is expected that the TLGL polytope will produce a cellular immune response. Therefore, the polytope could be a good candidate for an anti-leishmanial vaccine.

| S-EPMC7671421 | biostudies-literature

Bioinformatics analysis for the purpose of designing a novel multi-epitope DNA vaccine against Leishmania major.

Project description:Leishmaniasis is one of the main infectious diseases worldwide. In the midst of all the different forms of the disease, Cutaneous Leishmania (CL) has the highest incidence in the world. Many trial vaccines have been developed with the purpose of generating long-term cell-mediated immunity to Leishmania(L) major. As there is not any multi-epitope DNA vaccine with high efficacy against L.major, the aim of this study is to design a new multi-epitope DNA vaccine in order to have effective control upon this infectious disease through the immune bioinformatics. The L.major antigens: Gp63, LACK, TSA, LmSTI1and KMP11 were selected to design a multi-epitope DNA vaccine. The initial structure of the DNA vaccine was designed, benefiting from Gen Bank's website information. Epitopes of MHC-I antigens were predicted through the Immune Epitope Database (IEDB), and the selected epitopes were used to make vaccines construct along with linkers. New multi-epitope vaccine including 459 nucleic acids designed, and inserted between BamH1 and HindIII restriction sites of pCDNA3.1 mammalian expression vector. 12 epitopes among the chosen antigens were selected by two servers (IEDB and ANTIGEN). They had high stability and high antigenic power. Physicochemical features of vaccine measured by ProtParam server, and this structure was thermostable and hydrophilic. it's a suitable model to study on the animal and human phases. The designed vaccine is expected to be an effective candidate through development of (CL) vaccines. However, the effectiveness of this vaccine should also evaluate in vivo model.

| S-EPMC9612607 | biostudies-literature

Construction of a Novel DNA Vaccine Candidate encoding LmSTI1-PpSP42 Fusion Protein from Leishmania major and Phlebotomus papatasi against Cutaneous Leishmaniasis.

Project description:Background:Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical countries. The infection is caused by a protozoan parasite of Leishmania genus transmitted by Phlebotominae sandflies. In the present study, we constructed a eukaryotic expression vector to produce a fusion protein containing LmSTI1 from Leishmania major (L. major) and PpSP42 from Phlebotomus papatasi (Ph. papatasi). In future studies we will test this construct as a DNA vaccine against zoonotic CL. Methods:The nucleotide sequences encoding the LmSTI1 protein and a fragment encoding 79% of PpSP42 were amplified using L. major and Ph. papatasi genomic DNA, respectively. The amplicons were cloned into the pcDNA3.1(+) eukaryotic expression vector. The recombinant plasmid pcDNA-LmSTI1Pp42 was propagated in Escherichia coli (E. coli) and used to transfect HEK-293T cells. The expressed fusion protein was analyzed by Western blotting using anti-LmSTI1 mouse serum. Results:Sequences encoding LmSTI1 and partial PpSP42 were cloned into pcDNA3.1(+). Production of the recombinant LmSTI1Pp42 fusion protein was confirmed by Western blotting. Conclusion:An LmSTI1Pp42 fusion protein was expressed HEK-293T cells. This construct may be an effective DNA vaccine against CL.

| S-EPMC6175588 | biostudies-literature

In vitro evaluation of a soluble Leishmania promastigote surface antigen as a potential vaccine candidate against human leishmaniasis.

Project description:PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.

| S-EPMC4008367 | biostudies-literature

Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus.

Project description:Japanese encephalitis (JE) is a very severe disease characterized by high fatality rates and the development of permanent behavioral, psychiatric, and neurological sequelae among survivors. Japanese encephalitis virus (JEV), a flavivirus, is responsible for JE. In Asia, Genotype I (GI) has emerged as the dominant strain, replacing Genotype III (GIII). However, no clinically approved drug is available to treat JEV infection, and currently available commercial vaccines derived from JEV GIII strains provide only partial protection against GI. Utilizing a reverse genetics system, this study attempted to produce a novel chimeric JEV strain with high efficacy against JEV GI. Accordingly, a GI/GIII intertypic recombinant strain, namely SA14-GI env, was generated by substituting the E region of the GIII SA14-14-2 strain with that of the GI strain, K05GS. The neurovirulence of the mutant virus was significantly reduced in mice. Analysis of the immunogenicity of the chimeric virus revealed that it induced neutralizing antibodies against JEV GI in mice, and the protective efficacy of SA14-GI env was higher than that of SA14-14-2. These findings suggest that SA14-GI env may be a safe and effective live-attenuated vaccine candidate against JEV GI.

| S-EPMC10747704 | biostudies-literature

In silico analysis and in vivo assessment of a novel epitope-based vaccine candidate against uropathogenic Escherichia coli.

Project description:Uropathogenic Escherichia coli (UPEC) are common pathogens in urinary tract infections (UTIs), which show resistance to antibiotics. Therefore, there is a need for a vaccine to reduce susceptibility to the infection. In the present study, bioinformatics approaches were employed to predict the best B and T-cell epitopes of UPEC virulence proteins to develop a multiepitope vaccine candidate against UPEC. Then, the efficacy of the candidate was studied with and without Freund adjuvant. Using bioinformatics methods, 3 epitope-rich domains of IutA and FimH antigens were selected to construct the fusion. Molecular docking and Molecular dynamics (MD) simulation were employed to investigate in silico interaction between designed vaccine and Toll-like receptor 4 (TLR4). Our results showed that the levels of IgG and IgA antibodies were improved in the serum and mucosal samples of the vaccinated mice, and the IgG responses were maintained for at least 6 months. The fusion protein was also able to enhance the level of cytokines IFN.? (Th1), IL.4 (Th2), and IL.17. In challenge experiments, all vaccine combinations showed high potency in the protection of the urinary tract even after 6 months post first injection. The present study indicates that the designed candidate is able to evoke strong protective responses which warrant further studies.

| S-EPMC7530722 | biostudies-literature

In Silico Analysis of a Candidate Multi-epitope Peptide Vaccine Against Human Brucellosis.

Project description:Brucellosis is one of the neglected endemic zoonoses in the world. Vaccination appears to be a promising health strategy to prevent it. This study used advanced computational techniques to develop a potent multi-epitope vaccine for human brucellosis. Seven epitopes from four main brucella species that infect humans were selected. They had significant potential to induce cellular and humoral responses. They showed high antigenic ability without the allergenic characteristic. In order to improve its immunogenicity, suitable adjuvants were also added to the structure of the vaccine. The physicochemical and immunological properties of the vaccine were evaluated. Then its two and three-dimensional structure was predicted. The vaccine was docked with toll-like receptor4 to assess its ability to stimulate innate immune responses. For successful expression of the vaccine protein in Escherichia coli, in silico cloning, codon optimization, and mRNA stability were evaluated. The immune simulation was performed to reveal the immune response profile of the vaccine after injection. The designed vaccine showed the high ability to induce immune response, especially cellular responses to human brucellosis. It showed the appropriate physicochemical properties, a high-quality structure, and a high potential for expression in a prokaryotic system.

| S-EPMC10026239 | biostudies-literature

In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology.

Project description:Tuberculosis (TB) kills more individuals in the world than any other disease, and a threat made direr by the coverage of drug-resistant strains of Mycobacterium tuberculosis (Mtb). Bacillus Calmette-Guérin (BCG) is the single TB vaccine licensed for use in human beings and effectively protects infants and children against severe military and meningeal TB. We applied advanced computational techniques to develop a universal TB vaccine. In the current study, we select the very conserved, experimentally confirmed Mtb antigens, including Rv2608, Rv2684, Rv3804c (Ag85A), and Rv0125 (Mtb32A) to design a novel multi-epitope subunit vaccine. By using the Immune Epitopes Database (IEDB), we predicted different B-cell and T-cell epitopes. An adjuvant (Griselimycin) was also added to vaccine construct to improve its immunogenicity. Bioinformatics tools were used to predict, refined, and validate the 3D structure and then docked with toll-like-receptor (TLR-3) using different servers. The constructed vaccine was used for further processing based on allergenicity, antigenicity, solubility, different physiochemical properties, and molecular docking scores. The in silico immune simulation results showed significant response for immune cells. For successful expression of the vaccine in E. coli, in-silico cloning and codon optimization were performed. This research also sets out a good signal for the design of a peptide-based tuberculosis vaccine. In conclusion, our findings show that the known multi-epitope vaccine may activate humoral and cellular immune responses and maybe a possible tuberculosis vaccine candidate. Therefore, more experimental validations should be exposed to it.

| S-EPMC7807040 | biostudies-literature

In silico designing of vaccine candidate against Clostridium difficile.

Project description:Clostridium difficile is a spore-forming gram-positive bacterium, recognized as the primary cause of antibiotic-associated nosocomial diarrhoea. Clostridium difficile infection (CDI) has emerged as a major health-associated infection with increased incidence and hospitalization over the years with high mortality rates. Contamination and infection occur after ingestion of vegetative spores, which germinate in the gastro-intestinal tract. The surface layer protein and flagellar proteins are responsible for the bacterial colonization while the spore coat protein, is associated with spore colonization. Both these factors are the main concern of the recurrence of CDI in hospitalized patients. In this study, the CotE, SlpA and FliC proteins are chosen to form a multivalent, multi-epitopic, chimeric vaccine candidate using the immunoinformatics approach. The overall reliability of the candidate vaccine was validated in silico and the molecular dynamics simulation verified the stability of the vaccine designed. Docking studies showed stable vaccine interactions with Toll-Like Receptors of innate immune cells and MHC receptors. In silico codon optimization of the vaccine and its insertion in the cloning vector indicates a competent expression of the modelled vaccine in E. coli expression system. An in silico immune simulation system evaluated the effectiveness of the candidate vaccine to trigger a protective immune response.

| S-EPMC8271013 | biostudies-literature

A single-dose live attenuated chimeric vaccine candidate against Zika virus.

Project description:The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.

| S-EPMC7846741 | biostudies-literature

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