scholarly journals Identification of vaccine targets in pathogens and design of a vaccine using computational approaches

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kamal Rawal ◽  
Robin Sinha ◽  
Bilal Ahmed Abbasi ◽  
Amit Chaudhary ◽  
Swarsat Kaushik Nath ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Vaccine Development ◽  
Transmembrane Helix ◽  
Vaccine Antigen ◽  
Class I Mhc ◽  
Computational Approaches ◽  
Proteomic Dataset ◽  
Potential Vaccine ◽  
Informatics Tools

AbstractAntigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.

scholarly journals Scouting the receptor-binding domain of SARS coronavirus 2: a comprehensive immunoinformatics inquisition

2021 ◽  
Author(s):  
Zaira Rehman ◽  
Ammad Fahim ◽  
Muhammad Faraz Bhatti
Keyword(s):  
B Cell ◽  
Mhc Class Ii ◽  
Receptor Binding ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
T Cell Epitopes ◽  
Potential Vaccine ◽  
Spread Of Infection

Aim: December 2019 witnessed the emergence of a worldwide outbreak of a novel strain of coronavirus (CoV) termed SARS-CoV-2. Several preventive strategies are being developed, such as vaccines, to stop the spread of infection. Materials & methods: A comprehensive immunoinformatics approach was used to map conserved peptide sequences on the receptor binding domain of SARS-CoV-2 for their B-cell, T-helper & T-cytotoxic cell epitope profiles. Results & conclusion: The antigenic B-cell epitopes were LFRKSN and SYGFQPT. Among T-cell epitopes, CVADYSVLY and FTNVYADSF exhibited affinity for MHC class I, while YRLFRKSNL and VYAWNRKRI exhibited affinity for of MHC class II alleles. The overlapping epitope between B- and T-cells was YRLFRKSNL. The deployment of these epitopes in potential vaccine development against COVID-19 may help in slowing down the SARS-CoV-2 spread.

HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

2020 ◽  
Vol 28 ◽  
Author(s):  
Alireza Milani ◽  
Kazem Baesi ◽  
Elnaz Agi ◽  
Ghazal Marouf ◽  
Maryam Ahmadi ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Treated Group ◽  
Vaccine Antigen ◽  
Accessory Proteins ◽  
Serological Method ◽  
Th2 Immune Response ◽  
Untreated Individuals ◽  
Immunogenic Properties ◽  
Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

T-cell Epitope-based Vaccine Design for Nipah Virus by Reverse Vaccinology Approach

2020 ◽  
Vol 23 (8) ◽  
pp. 788-796
Author(s):  
Praveen K.P. Krishnamoorthy ◽  
Sekar Subasree ◽  
Udhayachandran Arthi ◽  
Mohammad Mobashir ◽  
Chirag Gowda ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Nipah Virus ◽  
3D Structure ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Reverse Vaccinology ◽  
Stable Complex

Aim and Objective: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and Methods: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T – cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T – cells. Conclusion: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

scholarly journals Coding as Literacy in Preschool: A Case Study

2021 ◽  
Vol 11 (5) ◽  
pp. 198
Author(s):  
Ana Francisca Monteiro ◽  
Maribel Miranda-Pinto ◽  
António José Osório
Keyword(s):  
Elementary Education ◽  
Developmentally Appropriate ◽  
Computational Thinking ◽  
School Subject ◽  
New Literacy ◽  
Computational Approaches ◽  
Knowledge Domains ◽  
And Robotics ◽  
Initial Framework

Coding is increasingly recognized as a new literacy that should be encouraged at a young age. This understanding has recontextualized computer science as a compulsory school subject and has informed several developmentally appropriate approaches to computation, including for preschool children. This study focuses on the introduction of three approaches to computation in preschool (3–6 years), specifically computational thinking, programming, and robotics, from a cross-curricular perspective. This paper presents preliminary findings from one of the case studies currently being developed as part of project KML II—Laboratory of Technologies and Learning of Programming and Robotics for Preschool and Elementary School. The purpose of the KML II project is to characterize how approaches to computation can be integrated into preschool and elementary education, across different knowledge domains. The conclusions point to “expression and communication” as an initial framework for computational approaches in preschool, but also to multidisciplinary and more creative methodological activities that offer greater scope for the development of digital and computational competences, as well as for personal and social development.

scholarly journals Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 692
Author(s):  
Giulia Franzoni ◽  
Antonio Anfossi ◽  
Chiara Grazia De Ciucis ◽  
Samanta Mecocci ◽  
Tania Carta ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Macrophage Polarization ◽  
Surface Protein ◽  
Antimicrobial Activities ◽  
Toll Like Receptor ◽  
Activation Markers ◽  
Class I Mhc ◽  
Toll Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

scholarly journals Exploiting the Reverse Vaccinology Approach to Design Novel Subunit Vaccine against Ebola Virus

2020 ◽  
Author(s):  
Md. Asad Ullah ◽  
Bishajit Sarkar ◽  
Syed Sajidul Islam
Keyword(s):  
Molecular Docking ◽  
Mhc Class Ii ◽  
Large Scale ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Rna Virus ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Molecular Docking Study ◽  
Class I Mhc

AbstractEbola virus is a highly pathogenic RNA virus that causes haemorrhagic fever in human. With very high mortality rate, Ebola virus is considered as one of the dangerous viruses in the world. Although, the Ebola outbreaks claimed many lives in the past, no satisfactory treatment or vaccine have been discovered yet to fight against Ebola. For this reason, in this study, various tools of bioinformatics and immunoinformatics were used to design possible vaccines against Zaire Ebola virus strain Mayinga-76. To construct the vaccine, three potential antigenic proteins of the virus, matrix protein VP40, envelope glycoprotein and nucleoprotein were selected against which the vaccines would be designed. The MHC class-I, MHC class-II and B-cell epitopes were determined and after robust analysis through various tools and molecular docking analysis, three vaccine candidates, designated as EV-1, EV-2 and EV-3, were constructed. Since the highly conserved epitopes were used for vaccine construction, these vaccine constructs are also expected to be effective on other strains of Ebola virus like strain Gabon-94 and Kikwit-95. Next, the molecular docking study on these vaccine constructs were analyzed by molecular docking study and EV-1 emerged as the best vaccine construct. Later, molecular dynamics simulation study revealed the good performances as well as good stability of the vaccine protein. Finally, codon adaptation and in silico cloning were conducted to design a possible plasmid (pET-19b plasmid vector was used) for large scale, industrial production of the EV-1 vaccine.

scholarly journals Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea A. Berry ◽  
Joshua M. Obiero ◽  
Mark A. Travassos ◽  
Amed Ouattara ◽  
Drissa Coulibaly ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Liver Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Iga Antibody ◽  
Potential Vaccine ◽  
Antigen Protein

AbstractKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

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