Prediction of Epitope Peptides for PTK Gene of Acinetobacter baumannii

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.

Specificity of Anti-Citrullinated Protein Antibodies to Citrullinated α-Enolase Peptides as a Function of Epitope Structure and Composition

Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1–2% of the world population. In addition to the first discovered serologic markers for RA, the rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs) are even more specific for the disease compared to RFs and are found in 70–80% of RA patient sera. RA etiopathogenesis still needs to be elucidated, as different factors are proposed to be involved, such as Epstein–Barr virus infection. Hence, understanding the interaction between ACPAs and their citrullinated peptide targets is relevant for a better knowledge of RA pathophysiology and for diagnostic purposes. In this study, a cohort of RA sera, healthy control sera and multiple sclerosis sera were screened for reactivity to a variety of citrullinated peptides originating from α-enolase, pro-filaggrin, proteoglycan and Epstein–Barr nuclear antigen-2 by enzyme-linked immunosorbent assay. ACPA reactivity to citrullinated α-enolase peptides was found to depend on peptide length and peptide conformation, favouring cyclic (disulfide bond) conformations for long peptides and linear peptides for truncated ones. Additional investigations about the optimal peptide conformation for ACPA detection, employing pro-filaggrin and EBNA-2 peptides, confirmed these findings, indicating a positive effect of cyclization of longer peptides of approximately 20 amino acids. Moreover, screening of the citrullinated peptides confirmed that ACPAs can be divided into two groups based on their reactivity. Approximately 90% of RA sera recognize several peptide targets, being defined as cross-reactive or overlapping reactivities, and whose reactivity to the citrullinated peptide is considered primarily to be backbone-dependent. In contrast, approximately 10% recognize a single target and are defined as nonoverlapping, primarily depending on the specific amino acid side-chains in the epitope for a stable interaction. Collectively, this study contributed to characterize epitope composition and structure for optimal ACPA reactivity and to obtain further knowledge about the cross-reactive nature of ACPAs.

In Silico Analysis of CadF Epitope-based Vaccine Design Against Campylobacter Jejuni

Objective: To eradicate infectious diseases, vaccination is an important strategy. CadF protein of Campylo bacter jejuni is one of the important factors in the process of the pathogenesis of the bacterium. So, the purpose of the work was to perform a bioinformatics study for identifying an epitope-based CadF vaccine, as a subunit vaccine. CadF sequences were extracted from the NCBI database. In silico analysis including all ergeni city, antigenicity, epitope conservancy assessment, molecular docking, etc.was done by different servers. Results:The results showed that CadF is an antigenic and non-allergenic protein and provides a suitable structure for vaccine design. Among epitopes, LSDSLALRL has been confirmed to stimulate both B and T cells. This 9-mers peptide is located in 135-143 segment of the CadF protein and interacted with HLA-A0101 and HLA-DRB1 0101 with energies of docking -26.18kcal/mol and -109.89kcal/mol. The peptide is not an allergen and as an antigen, it has the ability for motivating the immune system. Hence, the analyses are performed on that the epitope structure could verify the design of a vaccine against C. jejuni. The obtained theoretical results showed that CadF protein could be used for designing and evaluating a new vaccine in humans.

In silico Analysis of CadF epitope- based vaccine design against Campylobacter jejuni

Background To eradicate infectious diseases caused by microorganisms, vaccination is a popular strategy against them and can be an effective approach. Among vaccines, subunit vaccines have been used to be more effective against diseases. CadF protein of Campylobacter jejuni is one of the important antigens in the pathogenic process of the bacterium. So, the aim of this work was to do a bioinformatics study for the identification of epitope-based CadF vaccine, as a subunit vaccine. Main body CadF gene sequences were extracted from the NCBI database and suitable physic-chemical properties of CadF were evaluated by Protprom server. Some epitopes of the CadF protein with high affinity were detected by different servers, which were predicted based on MHC-peptide complex and B-cell epitopes. The results indicated that CadF is an antigenic and non-allergenic protein and provided a desirable structure for design vaccine. Among epitopes, LSDSLALRL was confirmed for the simulation of both of B and T cells. This 9-mers peptide was located in 135-143 sequences of CadF protein and interacted with HLA-A0101. The peptide isn’t allergen and has the ability to be an antigen for motivating immune system. Besides, the analysis implied that the epitope structure could allow designing a vaccine against C. jejuni.

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Avian influenza A(H9N2) viruses are an increasing threat to global poultry production and, through zoonotic infection, to human health where they are considered viruses with pandemic potential. Vaccination of poultry is a key element of disease control in endemic countries, but vaccine effectiveness is persistently challenged by the emergence of antigenic variants. Here we employed a combination of techniques to investigate the genetic basis of H9N2 antigenic variability and evaluate the role of different molecular mechanisms of immune escape. We systematically tested the influence of published H9N2 monoclonal antibody escape mutants on chicken antisera binding, determining that many have no significant effect. Substitutions introducing additional glycosylation sites were a notable exception, though these are relatively rare among circulating viruses. To identify substitutions responsible for antigenic variation in circulating viruses, we performed an integrated meta-analysis of all published H9 haemagglutinin sequences and antigenic data. We validated this statistical analysis experimentally and allocated several new residues to H9N2 antigenic sites providing molecular markers that will help explain vaccine breakdown in the field and inform vaccine selection decisions. We find evidence for the importance of alternative mechanisms of immune escape, beyond simple modulation of epitope structure, with substitutions increasing glycosylation or receptor-binding avidity exhibiting the largest impacts on chicken antisera binding. Of these, meta-analysis indicates avidity regulation to be more relevant to the evolution of circulating viruses, suggesting that a specific focus on avidity regulation is required to fully understand the molecular basis of immune escape by influenza, and potentially other viruses.