scholarly journals Leveraging Information Across HLA Alleles/Supertypes Improves Epitope Prediction

Author(s):  
David Heckerman ◽  
Carl Kadie ◽  
Jennifer Listgarten

Author(s):  
Romero-López JP ◽  
Carnalla-Cortés M ◽  
Pacheco-Olvera DL ◽  
Ocampo M ◽  
Oliva-Ramírez J ◽  
...  

Abstract SARS-CoV2 infection is causing a pandemic disease that is reflected in important public health problems worldwide. HLA-based epitope prediction and association with susceptibility provides an important base for treatment design. Hence the aim of this study is to predict the best antigen-presenting HLA-class I and II alleles in top affected populations and determine probable susceptibility associations. A bioinformatic prediction of T cell epitopes and their restricted HLA class I and II alleles was performed to predict immunogenic epitopes and HLA alleles from the spike protein of the SARS-CoV-2 virus, together with molecular modeling analysis and a correlation with the cumulative incidence of COVID-19 infection in 14 countries. Here, we describe a set of ten highly immunogenic epitopes, together with different HLA alleles that can efficiently present these epitopes to T cells. Most of these epitopes are located within the S1 subunit of the spike protein, suggesting that this area is highly immunogenic. A statistical correlation was found between the frequency of HLA-A*02:03 and HLA-A*31:01 and a low cumulative incidence in the selected countries.



2007 ◽  
Vol 14 (6) ◽  
pp. 736-746 ◽  
Author(s):  
David Heckerman ◽  
Carl Kadie ◽  
Jennifer Listgarten


2019 ◽  
Vol 2 (2) ◽  
pp. 1-17
Author(s):  
Sue-Mian Then ◽  
Azman Ali Raymond

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainly on the type of seizure. However, the use of AEDs may also lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discovered that the HLA-B*15:02 allele was strongly associated with carbamazepine (CBZ)-induced SJS/TEN among Han Chinese and this led to the discovery of other HLA alleles and cytochrome P450 (CYP) genes that were significantly associated with various AED-induced cADRs across various populations.  This mini review is an update on the latest findings of the involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamitrogine (LTG) in different case-control studies around the world. From our review, we found that CBZ- and PHT-induced cADRs were more commonly reported than the other AEDs. Therefore, there were more robust pharmacogenetics studies related to these AEDs. OXC- and LTG-induced cADRs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported HLA alleles with these AEDs. It is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for AED-induced cADR.



2020 ◽  
Vol 17 (5) ◽  
pp. 354-364
Author(s):  
Mohammad Mahmoudi Goumari ◽  
Ibrahim Farhani ◽  
Navid Nezafat ◽  
Shirin Mahmoodi

Infectious diseases have caused historical pandemics in the world. Three strategies, including sanitation programs, antimicrobial drugs, and vaccines are considered for the prevention and treatment of infectious diseases. Today, some infectious diseases cause millions of mortalities universally. Due to the emergence of antibiotic-resistant pathogens, as well as some limitations of traditional vaccines, focusing on novel strategies is essential. Multi-Epitope Vaccines (MEVs), as a novel strategy, have been designed based on immunoinformatics methods; epitope prediction by authentic servers, attachment of epitopes using proper linkers, physicochemical, immunological and structural evaluation by bioinformatics tools that are basic stages in MEVs designing. Advantages such as cost-effective, high safety, less time consumption in designing, the application of natural adjuvants, and satisfactory preclinical evaluation outstand MEVs than other types of vaccines. Therefore, MEVs are promising vaccines against resistant diseases such as lower respiratory infection and diarrhea.



2020 ◽  
Vol 17 ◽  
Author(s):  
Anam Naz ◽  
Tahreem Zaheer ◽  
Hamza Arshad Dar ◽  
Faryal Mehwish Awan ◽  
Ayesha Obaid ◽  
...  

Background: Helicobacter pylori infection and its treatment still remains a challenge to human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Aim of the study: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, and results in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabAHP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289-SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacAOmp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modelled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4. Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.



2019 ◽  
Vol 19 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Marzieh Rezaei ◽  
Mohammad Rabbani-khorasgani ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Rahman Emamzadeh ◽  
Hamid Abtahi

Background:Brucellosis is an infectious disease caused by Brucella bacteria that cause disease in animals and humans. Brucellosis is one of the most common zoonotic diseases transmitted from animals-to-human through direct contact with infected animals and also consumption of unpasteurized dairy products. Due to the wide incidence of brucellosis in Iran and economical costs in industrial animal husbandry, Vaccination is the best way to prevent this disease. All of the available commercial vaccines against brucellosis are derived from live attenuated strains of Brucella but because of the disadvantage of live attenuated vaccines, protective subunit vaccine against Brucella may be a good candidate for the production of new recombinant vaccines based on Brucella Outer Membrane Protein (OMP) antigens. In the present study, comprehensive bioinformatics analysis has been conducted on prediction software to predict T and B cell epitopes, the secondary and tertiary structures and antigenicity of Omp16 antigen and the validation of used software confirmed by experimental results.Conclusion:The final epitope prediction results have proposed that the three epitopes were predicted for the Omp16 protein with antigenicity ability. We hypothesized that these epitopes likely have the protective capacity to stimulate both the B-cell and T-cell mediated immune responses and so may be effective as an immunogenic candidate for the development of an epitope-based vaccine against brucellosis.



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