Abstract:Objectives
Dengue virus surface proteins are often used in the development of vaccines that protect against dengue virus infection. However, the surface proteins on the four serotypes of dengue virus display high variation, which increases the difficulty of developing a vaccine that can protect against all viral strains. In this study, a polytope that is recognized by broadly neutralizing antibodies (bnAbs) was designed using conserved epitopes from the four serotypes.
Methods
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“…It is reported that the conjugated polytope vaccine as a dendrimer constructed against HIV-1 elicited higher Th1 response [19]. In yet another instance, a polytope prediction from four conserved envelope protein of dengue virus serotypes was recognized by neutralizing IgGs [20]. Therefore, in this context, it is pertinent to build the molecular affinity based on spike protein sequences among the members of the family Coronaviridae and explore the possible multiepitope-based vaccine candidate for the population of Andhra Pradesh among Indian Asians.…”
Introduction:The rampant widespread of COVID-19 crossing continents in the year 2020 is primarily because of its unique spike protein architecture. Hence, the spike protein sequence similarities among the representatives of coronaviruses were evaluated so as to arrive at possible conservancy in its epitopes. Methods: Multiple sequence alignment and molecular phylogenetic analysis were done using MEGA software version X. Clustal omega open software was adapted to develop Percent Identity Matrix of spike proteins. Online IEDB tools were used to explore linear epitopes within the RBD region of spike protein of SARS CoV2 isolate of Wuhan-Hu-1 and their conservancy across the species of the chosen CoVs. Results: The constructed phylogenetic tree showed a primary cluster between SARS CoV2s of Wuhan and Bangladesh strains. The branch length of this primary cluster reflected their recency in emergence. Further, this primary cluster developed as an offshoot of yet another primary cluster between SARS CoV and bat SARS CoV. All betacoronaviruses grouped as one tertiary cluster, wherein MERS CoV formed as an independent offshoot and its branch length reflected that it is phylogenetically older. Both SARS CoV2s are the closest relatives to SARS CoV and Bat SARS CoV of China, and hence the similar pattern was confirmed through MEGA analysis. Ten linear epitopes were identified within the RBD region of the spike protein for the population of the State of Andhra Pradesh among Indian Asians based on their HLA haplotype diversity. Further, Conservancy Analysis of spike protein suggested that SARS CoV2 and SARS CoV shared 53% predicted epitopes. The physicochemical features of the envisaged polytope indicated the presence of 12.96% charged residues with instability index showing stable nature and more hydrophilicity as revealed through GRAVY values indicating that residues of polytope possibly interact well in aqueous environment. The secondary structure of the envisaged polytope showed predominantly coils, moderate number beta pleated sheets and α-helices with 41.2% residues in favoured region and 44.7% in allowed regions of Ramachandran Plot. Conclusion: The derived predicted scores of T-cell and B-cell immunogenicity, MHC class I binding, non-toxic and non-allergic due to the identified multi-epitope confirmed to be antigenic and elicit both T-cell and B-cell immune responses. Population coverage tool (IEDB) showed an adequate fraction of individuals predicted to respond to a given set of identified epitopes with known MHC restrictions in Indian Asian population.
“…It is reported that the conjugated polytope vaccine as a dendrimer constructed against HIV-1 elicited higher Th1 response [19]. In yet another instance, a polytope prediction from four conserved envelope protein of dengue virus serotypes was recognized by neutralizing IgGs [20]. Therefore, in this context, it is pertinent to build the molecular affinity based on spike protein sequences among the members of the family Coronaviridae and explore the possible multiepitope-based vaccine candidate for the population of Andhra Pradesh among Indian Asians.…”
Introduction:The rampant widespread of COVID-19 crossing continents in the year 2020 is primarily because of its unique spike protein architecture. Hence, the spike protein sequence similarities among the representatives of coronaviruses were evaluated so as to arrive at possible conservancy in its epitopes. Methods: Multiple sequence alignment and molecular phylogenetic analysis were done using MEGA software version X. Clustal omega open software was adapted to develop Percent Identity Matrix of spike proteins. Online IEDB tools were used to explore linear epitopes within the RBD region of spike protein of SARS CoV2 isolate of Wuhan-Hu-1 and their conservancy across the species of the chosen CoVs. Results: The constructed phylogenetic tree showed a primary cluster between SARS CoV2s of Wuhan and Bangladesh strains. The branch length of this primary cluster reflected their recency in emergence. Further, this primary cluster developed as an offshoot of yet another primary cluster between SARS CoV and bat SARS CoV. All betacoronaviruses grouped as one tertiary cluster, wherein MERS CoV formed as an independent offshoot and its branch length reflected that it is phylogenetically older. Both SARS CoV2s are the closest relatives to SARS CoV and Bat SARS CoV of China, and hence the similar pattern was confirmed through MEGA analysis. Ten linear epitopes were identified within the RBD region of the spike protein for the population of the State of Andhra Pradesh among Indian Asians based on their HLA haplotype diversity. Further, Conservancy Analysis of spike protein suggested that SARS CoV2 and SARS CoV shared 53% predicted epitopes. The physicochemical features of the envisaged polytope indicated the presence of 12.96% charged residues with instability index showing stable nature and more hydrophilicity as revealed through GRAVY values indicating that residues of polytope possibly interact well in aqueous environment. The secondary structure of the envisaged polytope showed predominantly coils, moderate number beta pleated sheets and α-helices with 41.2% residues in favoured region and 44.7% in allowed regions of Ramachandran Plot. Conclusion: The derived predicted scores of T-cell and B-cell immunogenicity, MHC class I binding, non-toxic and non-allergic due to the identified multi-epitope confirmed to be antigenic and elicit both T-cell and B-cell immune responses. Population coverage tool (IEDB) showed an adequate fraction of individuals predicted to respond to a given set of identified epitopes with known MHC restrictions in Indian Asian population.
Nowadays, dengue virus (DENV) is still become a global problem, even though the virus infection issues have reached half of the population in some countries each year. DENV belongs to the enveloped virus with positive-sense single-stranded RNA (+ssRNA) genus Flavivirus and belongs to the Flaviviridae family. DENV has structural proteins which consist of the envelope protein (E), capsid (C), and membrane (M). There are four serotypes of this virus which are DENV-1, 2, 3, and 4. These four serotypes are transmitted to humans through Aedes sp. The development of this vaccine is still in progress and the challenge of this DENV vaccine candidate design is to overcome the heterotypic infection and the expansion of coverage protection to all virus serotypes. This research uses design simulation for vaccine candidates using B cell epitope in all DENV’s serotypes envelope to trigger the antibody formation through bioinformatics method that consists of protein modeling, immunogenicity, toxicity, and immune stimulation. DENV envelope protein was predicted to have polytope that can be recognized by B cells and act as an antigen, have low similarity with the composing sequence of cell surface receptors on the body, and non-toxic, and then can trigger the population increase of B cell and IgM antibody production with high avidity to neutralize four of the DENV serotypes. We recommend the B cell polytype which consists of A, C, E, and G peptides be examined by the wet-lab approach.
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