Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study
Abstract Background Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to de...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12860-020-00334-6 |
| _version_ | 1818432776865579008 |
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| author | Davod Jafari Sara Malih Mohammad Mahmoudi Gomari Marzieh Safari Rasool Jafari Mohammad Morad Farajollahi |
| author_facet | Davod Jafari Sara Malih Mohammad Mahmoudi Gomari Marzieh Safari Rasool Jafari Mohammad Morad Farajollahi |
| author_sort | Davod Jafari |
| collection | DOAJ |
| description | Abstract Background Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to design a subunit chimeric vaccine from the antigenic and highly conserved regions of HA and M2 proteins of H7N9 subtype of influenza virus. We used mucosal adjuvant candidates, including CTxB, STxB, ASP-1, and LTB to stimulate mucosal immunity and analyzed the combination of HA2, M2e, and the adjuvant. Furthermore, to improve the antigen function and to maintain their three-dimensional structure, 12 different linkers including six rigid linkers and six flexible linkers were used. The 3D structure model was generated using a combination of homology and ab initio modeling methods and the molecular dynamics of the model were analyzed, either. Results Analysis of different adjuvants showed that using CtxB as an adjuvant, results in higher overall vaccine stability and higher half-life among four adjuvant candidates. Fusion of antigens and the CTxB in the form of M2e-linker-CTxB-linker-HA2 has the most stability and half life compared to other combination forms. Furthermore, the KPKPKP rigid linker showed the best result for this candidate vaccine among 12 analyzed linkers. The changes in the vaccine 3D structure made by linker insertion found to be negligible, however, although small, the linker insertion between the antigens causes the structure to change slightly. Eventually, using predictive tools such as Ellipro, NetMHCpan I and II, CD4episcore, CTLpred, BepiPred and other epitope analyzing tools, we analyzed the conformational and linear epitopes of the vaccine. The solubility, proteasome cleavage sites, peptidase and potential chemical cutters, codon optimization, post translational modification were also carried out on the final vaccine. Conclusions It is concluded that M2e-Linker-CTxB-Linker-HA2 combination of chimeric vaccine retains its 3D structure and antigenicity when KPKPKP used as linker and CTxB used as adjuvant. |
| first_indexed | 2024-12-14T16:10:35Z |
| format | Article |
| id | doaj.art-71e64e7e0db14378a62034ef28b4bf26 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-14T16:10:35Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-71e64e7e0db14378a62034ef28b4bf262022-12-21T22:55:01ZengBMCBMC Molecular and Cell Biology2661-88502020-12-0121111310.1186/s12860-020-00334-6Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics studyDavod Jafari0Sara Malih1Mohammad Mahmoudi Gomari2Marzieh Safari3Rasool Jafari4Mohammad Morad Farajollahi5Student Research Committee, Faculty of Allied Medicine, Iran University of Medical SciencesDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical SciencesDepartment of Microbiology, Faculty of Medicine, Isfahan University of Medical SciencesDepartment of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical SciencesStudent Research Committee, Faculty of Allied Medicine, Iran University of Medical SciencesAbstract Background Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to design a subunit chimeric vaccine from the antigenic and highly conserved regions of HA and M2 proteins of H7N9 subtype of influenza virus. We used mucosal adjuvant candidates, including CTxB, STxB, ASP-1, and LTB to stimulate mucosal immunity and analyzed the combination of HA2, M2e, and the adjuvant. Furthermore, to improve the antigen function and to maintain their three-dimensional structure, 12 different linkers including six rigid linkers and six flexible linkers were used. The 3D structure model was generated using a combination of homology and ab initio modeling methods and the molecular dynamics of the model were analyzed, either. Results Analysis of different adjuvants showed that using CtxB as an adjuvant, results in higher overall vaccine stability and higher half-life among four adjuvant candidates. Fusion of antigens and the CTxB in the form of M2e-linker-CTxB-linker-HA2 has the most stability and half life compared to other combination forms. Furthermore, the KPKPKP rigid linker showed the best result for this candidate vaccine among 12 analyzed linkers. The changes in the vaccine 3D structure made by linker insertion found to be negligible, however, although small, the linker insertion between the antigens causes the structure to change slightly. Eventually, using predictive tools such as Ellipro, NetMHCpan I and II, CD4episcore, CTLpred, BepiPred and other epitope analyzing tools, we analyzed the conformational and linear epitopes of the vaccine. The solubility, proteasome cleavage sites, peptidase and potential chemical cutters, codon optimization, post translational modification were also carried out on the final vaccine. Conclusions It is concluded that M2e-Linker-CTxB-Linker-HA2 combination of chimeric vaccine retains its 3D structure and antigenicity when KPKPKP used as linker and CTxB used as adjuvant.https://doi.org/10.1186/s12860-020-00334-6AdjuvantBioinformaticsEpitopesHemagluttininInfluenza a virusVaccine design |
| spellingShingle | Davod Jafari Sara Malih Mohammad Mahmoudi Gomari Marzieh Safari Rasool Jafari Mohammad Morad Farajollahi Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study BMC Molecular and Cell Biology Adjuvant Bioinformatics Epitopes Hemagluttinin Influenza a virus Vaccine design |
| title | Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study |
| title_full | Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study |
| title_fullStr | Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study |
| title_full_unstemmed | Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study |
| title_short | Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study |
| title_sort | designing a chimeric subunit vaccine for influenza virus based on ha2 m2e and ctxb a bioinformatics study |
| topic | Adjuvant Bioinformatics Epitopes Hemagluttinin Influenza a virus Vaccine design |
| url | https://doi.org/10.1186/s12860-020-00334-6 |
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