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Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate against Onchocerciasis and Related Filarial Diseases.

ABSTRACT: : Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-?, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis.

SUBMITTER: Shey RA

PROVIDER: S-EPMC7912539 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:COVID-19 caused by SARS-CoV-2 was declared a global pandemic by WHO (World Health Organization) in March, 2020. Within 6 months, nearly 750,000 deaths are claimed by COVID-19 across the globe. This called for immediate social, scientific, technological, public and community interventions. Considering the severity of infection and the associated mortalities, global efforts are underway to develop preventive measures against SARS-CoV-2. Among the SARS-CoV-2 target proteins, Spike (S) glycoprotein (a.k.a S Protein) is the most studied target known to trigger strong host immune response. A detailed analysis of S protein-based epitopes enabled us to design a novel B-cell-derived T-cell Multi-epitope-based peptide (MEBP) vaccine candidate. This involved a systematic and comprehensive computational protocol consisting of prediction of dual-purpose epitopes and designing an MEBP vaccine construct. This was followed by 3D structure validation, MEBP complex interaction studies, in silico cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The dual-purpose epitope prediction protocol was designed such that the same epitope elicits both humoral and cellular immune response unlike the earlier designs. Further, the epitopes predicted were screened against stringent criteria to ensure selection of a potent candidate with maximum antigen coverage and best immune response. The vaccine dose-based immune response simulation studies revealed a rapid antigen clearance through antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis strongly indicate that the vaccine construct is indeed a potent vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-020-02574-x.

Project description:The discovery of a new SARS-CoV-2 virus strain in South Africa presents a major public health threat, therefore contributing to increased infections and transmission rates during the second wave of the global pandemic. This study lays the groundwork for the development of a novel subunit vaccine candidate from the circulating strains of South African SARS-CoV-2 and provides an understanding of the molecular epidemiological trend of the circulating strains. A total of 475 whole-genome nucleotide sequences from South Africa submitted between December 1, 2020 and February 15, 2021 available at the GISAID database were retrieved based on its size, coverage level and hosts. To obtain the distribution of the clades and lineages of South African SARS-CoV-2 circulating strains, the metadata of the sequence retrieved were subjected to an epidemiological analysis. There was a prediction of the cytotoxic T lymphocytes (CTL), Helper T cells (HTL) and B-cell epitopes. Furthermore, there was allergenicity, antigenicity and toxicity predictions on the epitopes. The analysis of the physicochemical properties of the vaccine construct was performed; the secondary structure, tertiary structure and B-cell 3D conformational structure of the vaccine construct were predicted. Also, molecular binding simulations and dynamics simulations were adopted in the prediction of the vaccine construct's stability and binding affinity with TLRs. Result obtained from the metadata analysis indicated lineage B.1.351 to be in higher circulation among various circulating strains of SARS-CoV-2 in South Africa and GH has the highest number of circulating clades. The construct of the novel vaccine was antigenic, non-allergenic and non-toxic. The Instability index (II) score and aliphatic index were estimated as 41.74 and 78.72 respectively. The computed half-life in mammalian reticulocytes was 4.4 h in vitro, for yeast and in E. coli was >20 h and >10 h in vivo respectively. The grand average of hydropathicity (GRAVY) score is estimated to be -0.129, signifying the hydrophilic nature of the protein. The molecular docking indicates that the vaccine construct has a high binding affinity towards the TLRs with TLR 3 having the highest binding energy (-1203.2 kcal/mol) and TLR 9 with the lowest (-1559.5 kcal/mol). These results show that the vaccine construct is promising and should be evaluated using animal model.

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Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate against Onchocerciasis and Related Filarial Diseases.

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