scholarly journals Prediction of Epitope Peptides for PTK Gene of Acinetobacter baumannii

Author(s):  
M. I. Sheefaa ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini

Background: Acinetobacter baumannii is a gramnegative bacilli acquiring both intrinsic and adaptive patterns of multi drug resistance and virulence. Immune-informatics approach holds promise to detect putative epitope peptides from vital virulence factors which can be further synthesized and evaluated for their immunological response. Aim: The aim of the study was to predict the immuno-dominant peptides from the ptk gene of A. baumannii. Materials and Methods: Protein retrieval of the Ptk gene using CELLO V.2.5 was done with the evaluation of antigenicity and allergenicity of the predicted epitopes, using Vaxijen V2.0 server and AlgPred servers. Epitope structure prediction and validation by using RAMPAGE revealed the homology peptides. Molecular Docking of epitopes with HLA-alleles using ClusterPro server, and further identification of B cell epitope was performed by using Kolaskar and Tonganokar antigenicity method. Results: A total of 20 epitopes were predicted and 18 peptides were chosen based on antigenicity and stability analysis prediction. The structure predictions were carried out using pepfold server and based on Ramachandran plot analysis 10 epitopes were taken for further analysis. Conclusion: The present finding has detected and evaluated the desirable epitope as LFFSLIAQW using an immune-informatic approach. However, it needs further experimental validation for its immunological response using standard in-vitro studies.

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaojie Song ◽  
Guanghui Zhao ◽  
Meiling Ding

Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen widely present in medical environment. Given its complex drug resistance, A. baumannii poses a serious threat to the safety of critically ill patients. Given the limited alternative antibiotics, nonantibiotic-based functional anti-A. baumannii infection proteins must be developed. In this study, we firstly used a series of biological software to predict potential epitopes in the MacB protein sequence and verified them by antibody recognition and lymphocyte proliferation tests. We finally screened out B cell epitope 2, CD8+ T cell epitope 7, and CD4+ T cell epitope 11 and connected them to construct a recombinant antigen epitope (RAE). The determination of IgG in the serum of immunised mice and cytokines in the supernatant of lymphocytes showed that the constructed epitope induced an immune response mediated by Th-1 cells. Finally, the challenge experiment of A. baumannii infection in mice confirmed that the epitope developed based on MacB, especially RAE, provided incomplete immune protection for mice.


2016 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Seyed Sajjad Hasheminasab ◽  
Hossein Maghsood ◽  
Sara Khalili

<p class="MsoNormal" style="text-align: justify; text-justify: inter-ideograph;"><span style="font-size: 9.0pt;">Toxoplasmosis is one of the most widespread infections in animals and humans. The <em>Toxoplasma gondii</em> major surface antigen, called SAG1 or p30, is a highly immunogenic protein which has generated great interest as a diagnostic reagent, as a potential subunit vaccine, and for its role in invasion. In this study, the epitopes of <em>Toxoplasma gondii</em> SAG1 were identified using bioinformatics. Through the analysis of the out¬put of both NetCTL and CTLPred, and B-cell epitope prediction, the position of all the epitopes were found and combined in four sequences. The different tasks including, T-cell and B-cell prediction, Antigenicity determination of the conserved peptides, Homology modeling, Allergenicity and epitope conservancy analysis were done on the conserved peptides. We predict that our proposed epitopes would also trigger an immune response in vitro.</span></p><span style="font-size: 18.0pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: Batang; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">Immunoinformatic prediction about potential novel vaccine in surface antigen fragment protein of <em>Toxoplasma gondii</em></span>


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mohammad Tuhin Ali ◽  
Md Ohedul Islam

Ebola virus (EBOV) is a deadly virus that has caused several fatal outbreaks. Recently it caused another outbreak and resulted in thousands afflicted cases. Effective and approved vaccine or therapeutic treatment against this virus is still absent. In this study, we aimed to predict B-cell epitopes from several EBOV encoded proteins which may aid in developing new antibody-based therapeutics or viral antigen detection method against this virus. Multiple sequence alignment (MSA) was performed for the identification of conserved region among glycoprotein (GP), nucleoprotein (NP), and viral structural proteins (VP40, VP35, and VP24) of EBOV. Next, different consensus immunogenic and conserved sites were predicted from the conserved region(s) using various computational tools which are available in Immune Epitope Database (IEDB). Among GP, NP, VP40, VP35, and VP30 protein, only NP gave a 100% conserved GEQYQQLR B-cell epitope that fulfills the ideal features of an effective B-cell epitope and could lead a way in the milieu of Ebola treatment. However, successful in vivo and in vitro studies are prerequisite to determine the actual potency of our predicted epitope and establishing it as a preventing medication against all the fatal strains of EBOV.


1985 ◽  
Vol 162 (1) ◽  
pp. 311-323 ◽  
Author(s):  
U Krzych ◽  
A V Fowler ◽  
E E Sercarz

11 cyanogen bromide (CB) peptides, comprising 70% of the large protein, Escherichia coli beta-galactosidase (GZ), were studied for their ability to induce T suppressor (Ts) cells capable of strongly suppressing the in vitro anti-fluorescein (FITC) response to GZ-FITC. Only CB-2 (amino acid residues 3-92) and CB-3 (residues 93-187) were found to bear such Ts-inducing epitopes. In examining the specificity of T helper cell (Th) targets susceptible to CB-2 and CB-3-specific Ts, it appeared that only nearly Th targets could be suppressed. Thus, CB-10-primed Th were not suppressed by either Ts; even CB-3-primed Ts did not suppress CB-2-specific Th, although CB-2-specific Ts were effective. Furthermore, analysis of the suppression pattern revealed a hierarchical use of potential epitopes on native GZ in triggering functional regulatory T cells. A dominant Th epitope near the amino terminus of GZ tops a hierarchy of potential Th, most of which are never engaged. The dominant determinant seems to exist on the peptide CB-2-3 (residues 3-187), and presumably is destroyed by its cleavage at Met 92; the Th cells that it induces are suppressible by each of the Ts-inducing peptides. In the GZ system, where the native antigen is quite large, the interactions between Th and Ts are highly circumscribed. This may be attributable to the topology of antigen fragments produced during processing; any relevant fragment must bear at least a Ts- and Th-reactive determinant to permit intercellular regulation. A final implication of these results is that, not only does the existence of a Th-inducing determinant depend on its being an appropriate distance from a B cell epitope, but the existence of Ts-inducing determinants likewise depends on the existence of a neighboring Th-B cell association.


2020 ◽  
Author(s):  
Renu Jakhar ◽  
S.K Gakhar

AbstractCOVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S628-S629
Author(s):  
Dhammika Leshan Wannigama ◽  
Paul G Higgins ◽  
Cameron Hurst ◽  
Shuichi Abe ◽  
Parichart Hongsing ◽  
...  

Abstract Background Due to the increase in multi-drug resistance (MDR) of Acinetobacter baumannii chronic infections with accompanying considerable morbidity and mortality, it is imperative to find effective novel treatments. Durlobactam (DUR) is a potent broad-spectrum inhibitor of Ambler classes A, C and D serine β-lactamases that effectively restores sulbactam (SUL) activity against MDR A.baumannii isolates. SUL-DUR is currently in late-stage development for the treatment of infections caused by Acinetobacter spp., including drug resistant isolates. In this study, we sought to evaluate potency of SUL-DUR against MDR A. baumannii isolates collected from Thai patients with chronic infections. Methods Non-duplicative clinical strains were isolated during 2016–2019 from 200 chronically infected patients in different medical wards with a variety of different infections at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Susceptibility testing of SUL-DUR and comparator agents was performed according to CLSI guidelines. SUL-DUR was also tested on a background of imipenem (IPM) therapy (SUL-IPM titrated at a 1:1 ratio plus DUR fixed at 4 mg/L). Data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 92% sulbactam-resistant (using a breakpoint of 4 mg/L), 91% carbapenem-resistant, 74% amikacin resistant and 8% colistin resistant. In contrast, the SUL-DUR MIC90 was 4 mg/L compared with 64 mg/L for sulbactam alone. SUL-DUR was equally potent across antibiotic-resistant subsets. Only 6 isolates (3%) had SUL-DUR MIC values &gt;4 mg/L. Interestingly, addition of imipenem to SUL-DUR showed similar potency as SUL-DUR alone, with an MIC90 of 2 mg/L. Conclusion SUL-DUR showed potent in vitro activity against contemporary clinical isolates from a hospital in Bangkok, Thailand. If successfully developed, SUL-DUR may be an important new therapeutic option for the treatment of MDR Acinetobacter infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee)


2018 ◽  
Author(s):  
Saruar Alam ◽  
Md. Kamrul Hasan ◽  
Md. Faruk Hossain

AbstractProfilin is an actin monomer-binding protein that controls the dynamic turnover of actin filaments and is ubiquitously present in different organisms ranging from prokaryotes to higher eukaryotes. Maize (Zea mays) profilin-4 isoform is a pollen-specific protein. Birch profilin isoform is a known allergen but maize profilin is yet to be characterized. Due to the high cultivation rate of maize, the analysis of the properties of maize profilin-4 isoform as an allergen is a demand of time for developing an effective immune therapy. Here, we analyzed the allergenic potency of profilin-4 by studying of its physicochemical properties, including molecular weight (∼14kD) and theoretical pI (4.63). We tested the potential B cell epitope candidates of profilin-4 using different immune-informatics tools housed at IEDB analysis resource. For the B cell epitope prediction, potential antigenic sites on the protein surface were predicted by both propensity scale and machine learning method followed by their mapping of 3D structure prediction. We hereby claim that the profilin-4 is a potential allergen and is able to induce allergic responses. However, the wet lab experiments are needed to validate our claim that’s beyond our scope.


2021 ◽  
Vol 11 ◽  
Author(s):  
Patricia de León ◽  
Rodrigo Cañas-Arranz ◽  
Sira Defaus ◽  
Elisa Torres ◽  
Mar Forner ◽  
...  

Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B2T-3A and B2T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B2TT-3A3D and B2TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B2TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B2TT-3A3D. Pigs immunized with B2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4+ T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4+ cells from PBMCs abolished the production of this cytokine. Most CD4+IFN-γ+ cells showed a memory (CD4+2E3−) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B2TT-3D3A and B2 groups had fewer cells expressing both cytokines. These results help understand how B2T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258637
Author(s):  
Raianna F. Fantin ◽  
Vanessa G. Fraga ◽  
Camila A. Lopes ◽  
Isabella C. de Azevedo ◽  
João L. Reis-Cunha ◽  
...  

Peptide-based vaccines have demonstrated to be an important way to induce long-lived immune responses and, therefore, a promising strategy in the rational of vaccine development. As to malaria, among the classic vaccine targets, the Apical membrane antigen (AMA-1) was proven to have important B cell epitopes that can induce specific immune response and, hence, became key players for a vaccine approach. The peptides selection was carried out using a bioinformatic approach based on Hidden Markov Models profiles of known antigens and propensity scale methods based on hydrophilicity and secondary structure prediction. The antigenicity of the selected B-cell peptides was assessed by multiple serological assays using sera from acute P.vivax infected subjects. The synthetic peptides were recognized by 45.5%, 48.7% and 32.2% of infected subjects for peptides I, II and III respectively. Moreover, when synthetized together (tripeptide), the reactivity increases up to 62%, which is comparable to the reactivity found against the whole protein PvAMA-1 (57%). Furthermore, IgG reactivity against the tripeptide after depletion was reduced by 42%, indicating that these epitopes may be responsible for a considerable part of the protein immunogenicity. These results represent an excellent perspective regarding future chimeric vaccine constructions that may come to contemplate several targets with the potential to generate the robust and protective immune response that a vivax malaria vaccine needs to succeed.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Stanislava Yu. Petrova ◽  
Svetlana V. Khlgatian ◽  
Elena V. Svirshchevskaya ◽  
Anna V. Vasilyeva ◽  
Valentina M. Berzhets

This review is intended to familiarize readers with major novel directions of developing allergy vaccines, their structure, as well as the mechanisms of forming a new immunological response in the course of the treating immunoglobulin E (IgE)-mediated allergic diseases. Currently, science offers a huge variety of new experimental forms of recombinant allergens with reduced allergenic activity and increased immunogenicity, or vice-versa, immune tolerance. Often, the mechanisms of their effect on the immune system are not fully understood. Scientific publications, including reviews covering this topic, allowed us identifying top priority areas in the development of allergy vaccines: recombinant hypoallergenic allergen derivatives, T cell epitope-based allergy vaccines, and B cell epitope-based allergy vaccines. In addition, the review discusses use of deoxyribonucleic acid (DNA) vaccines. Immunotherapy with DNA vaccines is the newest and least studied method of treating allergic diseases.


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