Exploring the Zika Genome to Design a Potential Multiepitope Vaccine Using an Immunoinformatics Approach

Mittal, Ayushi; Sasidharan, Santanu; Raj, Shweta; Balaji, S.; Saudagar, Prakash

doi:10.1007/s10989-020-10020-y

Cited by 20 publications

(12 citation statements)

References 38 publications

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“…In the present study, EAAAK linker was attached at the N-terminal end of the vaccine construct (Mittal et al., 2020 ; Sarkar et al., 2020 ) and was also used to join the β-defensin sequence with PADRE sequence (Sarkar et al., 2020 ). EAAAK is a rigid α-helix forming peptide linker, with intramolecular hydrogen bonding having a closed packed backbone.…”

Section: Resultsmentioning

confidence: 99%

Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach

Ayyagari

Venkateswarulu

et al. 2020

Journal of Biomolecular Structure and Dynamics

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In the present study, one of the targets present on the envelopes of coronaviruses, membrane glycoprotein (M) was chosen for the design of a multi-epitope vaccine by Immunoinformatics approach. The B-cell and T-cell epitopes used for the construction of vaccine were antigenic, nonallergic and nontoxic. An adjuvant, b-defensin and PADRE sequence were included at the N-terminal end of the vaccine. All the epitopes were joined by linkers for decreasing the junctional immunogenicity. Various physicochemical parameters of the vaccine were evaluated. Secondary and tertiary structures were predicted for the vaccine construct. The tertiary structure was further refined, and various parameters related to the refinement of the protein structure were validated by using different tools. Humoral immunity induced by B-cells relies upon the identification of antigenic determinants on the surface of the vaccine construct. In this regard, the vaccine construct was found to consist of several B-cell epitopes in its three-dimensional conformation. Molecular docking of the vaccine was carried out with TLR-3 receptor to study their binding and its strength. Further, protein-protein interactions in the docked complex were visualized using LigPlotþ. Population coverage analysis had shown that the multi-epitope vaccine covers 94.06% of the global population. The vaccine construct was successfully cloned in silico into pET-28a (þ). Immune simulation studies showed the induction of primary, secondary and tertiary immune responses marked by the increased levels of antibodies, INF-c, IL-2, TGF-b, B-cells, CD4þ and CD8þ cells. Finally, the vaccine construct was able to elicit immune response as desired.

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Section: Resultsmentioning

confidence: 99%

Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach

Ayyagari

Venkateswarulu

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…The study presented, herein, is an attempt to get insights about antigenic determinants of SARS-CoV-2 spike glycoprotein and highlight all antigenic epitopes [31] of the spike that can be used specifically for the design of a multi-epitope peptide vaccine construct (MEPVC) [32]to counter COVID-19 infections. The epitopes predicted by immunoinformatics techniques were fused together as well as to β-defensin adjuvant [33,34] to boost the antibody production and long-…”

Section: Introductionmentioning

confidence: 99%

Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine

Ismail

Ahmad

Azam

2020

Preprint

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The COVID-19 pandemic caused by SARS-CoV-2 is a public-health emergency of international concern and thus calling for the development of safe and effective therapeutics and prophylactics particularly a vaccine to protect against the infection. SARS-CoV-2 spike glycoprotein is an attractive candidate for vaccine, antibodies and inhibitor development because of many roles it plays in attachment, fusion and entry into the host cell. In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). The MEPVC revealed robust host immune system simulation with high production of immunoglobulins, cytokines and interleukins. Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. Molecular dynamics simulation in solution aided further in interpreting strong affinity of the MEPVC for TLR3. This stability is the attribute of several vital residues from both TLR3 and MEPVC as shown by radial distribution function (RDF) and a novel analytical tool axial frequency distribution (AFD). Comprehensive binding free energies estimation was provided at the end that concluded major domination by electrostatic and minor from van der Waals. Summing all, the designed MEPVC has tremendous potential of providing protective immunity against COVID-19 and thus has the potential to be considered in experimental studies.

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“…β-defensin was also attached as an adjuvant to the first CTL epitope via the EAAAK linker. Owing to the good antimicrobial and immunomodulatory properties, β-defensin acts as a very good adjuvant [ 83 ] and it has been used in many previous reported studies [ 84 , 85 ]. Multiepitope-based subunit vaccines need adjuvant coupling to enhance their immunogenicity [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design

et al. 2021

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Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in curing disease. For this purpose, an immuno-informatics study is performed based on the published HCV subtype-3a from Pakistan. First, the virus genome was translated to a polyprotein followed by a subsequent prediction of T-cell epitopes. Non-allergenic, IFN-γ producer, and antigenic epitopes were shortlisted, including 5 HTL epitopes and 4 CTL, which were linked to the final vaccine by GPGPG and AAY linkers, respectively. Beta defensin was included as an adjuvant through the EAAAK linker to improve the immunogenicity of the polypeptide. To ensure its safety and immunogenicity profile, antigenicity, allergenicity, and various physiochemical attributes of the polypeptide were evaluated. Molecular docking was conducted between TLR4 and vaccine to evaluate the binding affinity and molecular interactions. For stability assessment and binding of the vaccine-TLR4 docked complex, molecular dynamics (MD) simulation and MMGBSA binding free-energy analyses were conducted. Finally, the candidate vaccine was cloned in silico to ensure its effectiveness. The current vaccine requires future experimental confirmation to validate its effectiveness. The vaccine construct produced might be useful in providing immune protection against HCV-related infections.

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Exploring the Zika Genome to Design a Potential Multiepitope Vaccine Using an Immunoinformatics Approach

Cited by 20 publications

References 38 publications

Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach

Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach

Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine

Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design

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