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Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences.

ABSTRACT: Background:The coronavirus SARS-CoV-2 is a member of the Coronaviridae family that has caused a global public health emergency. Currently, there is no approved treatment or vaccine available against it. The current study aimed to cover the diversity of SARS-CoV-2 strains reported from all over the world and to design a broad-spectrum multi-epitope vaccine using an immunoinformatics approach. Methods:For this purpose, all available complete genomes were retrieved from GISAID and NGDC followed by genome multiple alignments to develop a global consensus sequence to compare with the reference genome. Fortunately, comparative genomics and phylogeny revealed a significantly high level of conservation between the viral strains. All the Open Reading Frames (ORFs) of the reference sequence NC_045512.2 were subjected to epitope mapping using CTLpred and HLApred, respectively. The predicted CTL epitopes were then screened for antigenicity, immunogenicity and strong binding affinity with HLA superfamily alleles. HTL predicted epitopes were screened for antigenicity, interferon induction potential, overlapping B cell epitopes and strong HLA DR binding potential. The shortlisted epitopes were arranged into two multi-epitope sequences, Cov-I-Vac and Cov-II-Vac, and molecular docking was performed with Toll-Like Receptor 8 (TLR8). Results:The designed multi-epitopes were found to be antigenic and non-allergenic. Both multi-epitopes were stable and predicted to be soluble in an Escherichia coli expression system. The molecular docking with TLR8 also demonstrated that they have a strong binding affinity and immunogenic potential. These in silico analyses suggest that the proposed multi-epitope vaccine can effectively evoke an immune response.

SUBMITTER: Zaheer T

PROVIDER: S-EPMC7409810 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences.

Zaheer Tahreem T Waseem Maaz M Waqar Walifa W Dar Hamza Arshad HA Shehroz Muhammad M Naz Kanwal K Ishaq Zaara Z Ahmad Tahir T Ullah Nimat N Bakhtiar Syeda Marriam SM Muhammad Syed Aun SA Ali Amjad A

PeerJ 20200803

<h4>Background</h4>The coronavirus SARS-CoV-2 is a member of the Coronaviridae family that has caused a global public health emergency. Currently, there is no approved treatment or vaccine available against it. The current study aimed to cover the diversity of SARS-CoV-2 strains reported from all over the world and to design a broad-spectrum multi-epitope vaccine using an immunoinformatics approach.<h4>Methods</h4>For this purpose, all available complete genomes were retrieved from GISAID and NG ...[more]

PMID: 32832263

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Project description:COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1-14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.

Project description:BackgroundEpitope vaccines have been suggested as a strategy to counteract viral escape and development of drug resistance. Multiple studies have shown that Cytotoxic T-Lymphocyte (CTL) and T-Helper (Th) epitopes can generate strong immune responses in Human Immunodeficiency Virus (HIV-1). However, not much is known about the relationship among different types of HIV epitopes, particularly those epitopes that can be considered potential candidates for inclusion in the multi-epitope vaccines.ResultsIn this study we used association rule mining to examine relationship between different types of epitopes (CTL, Th and antibody epitopes) from nine protein-coding HIV-1 genes to identify strong associations as potent multi-epitope vaccine candidates. Our results revealed 137 association rules that were consistently present in the majority of reference and non-reference HIV-1 genomes and included epitopes of two different types (CTL and Th) from three different genes (Gag, Pol and Nef). These rules involved 14 non-overlapping epitope regions that frequently co-occurred despite high mutation and recombination rates, including in genomes of circulating recombinant forms. These epitope regions were also highly conserved at both the amino acid and nucleotide levels indicating strong purifying selection driven by functional and/or structural constraints and hence, the diminished likelihood of successful escape mutations.ConclusionsOur results provide a comprehensive systematic survey of CTL, Th and Ab epitopes that are both highly conserved and co-occur together among all subtypes of HIV-1, including circulating recombinant forms. Several co-occurring epitope combinations were identified as potent candidates for inclusion in multi-epitope vaccines, including epitopes that are immuno-responsive to different arms of the host immune machinery and can enable stronger and more efficient immune responses, similar to responses achieved with adjuvant therapies. Signature of strong purifying selection acting at the nucleotide level of the associated epitopes indicates that these regions are functionally critical, although the exact reasons behind such sequence conservation remain to be elucidated.

Project description:The family members of Arenaviridae include members of the genus Machupo virus, which have bi-segmented negative sense RNA inside the envelope and can be transferred to humans through rodent carriers. Machupo virus, a member of the mammarenavirus genus, causes Bolivian hemorrhage fever, its viral nucleocapsid protein being a significant virulence factor. Currently, no treatment is available for Bolivian hemorrhage fever and work to develop a protective as well as post-diagnosis treatment is underway. Adding to these efforts, this study employed a reverse-vaccinology approach to design a vaccine with B and T-cell epitopes of the viral nucleocapsid protein of the Machupo virus. Five B-cell specific, eight MHC-I restricted, and 14 MHC-II restricted epitopes were finalized for the construct based on an antigenicity score of >0.5 and non-allergenicity as a key characteristic. The poly-histidine tag was used to construct an immunogenic and stable vaccine construct and 50S ribosomal 46 protein L7/L12 adjuvant with linkers (EAAAK, GPGPG, and AYY). It covers 99.99% of the world's population, making it highly efficient. The physicochemical properties like the aliphatic index (118.31) and the GRAVY index (0.302) showed that the vaccine is easily soluble. The overall Ramachandran score of the construct was 90.7%, and the instability index was 35.13, endorsing a stable structure. The immune simulations demonstrated a long-lasting antibody response even after the excretion of the antigen from the body in the first 5 days of injection. The IgM + IgG titers were predicted to rise to 6000 10 days post-injection and were illustrated to be stable (around 3000) after a month, elucidating that the vaccine would be effective and provide enduring protection. Lastly, the molecular interaction between the construct and the IKBKE receptor was significant and a higher eigenfactor value in MD simulations confirmed the stable molecular interaction between the receptor and the vaccine, validating our construct.

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Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences.

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Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences.

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