作者
Shiyang Ma,Fei Zhu,Haicheng Wen,Mingjun Rao,Peipei Zhang,Wenzhong Peng,Yanhui Cui,Hang Yang,Caixia Tan,Jie Chen,Pinhua Pan
摘要
AbstractChikungunya virus (CHIKV), a type A virus borne by mosquitoes that can cause major clinical manifestations including rash, fever and debilitating arthritis, grown into a reemerging serious public health issue. Currently, there is no licensed therapy or vaccine available for CHIKV, although the most promising form of treatment appears to be immunotherapy. Neutralizing antibodies for CHIKV can provide high protection for all CHIKV strains, as well as other alphaviruses. Development of a protective vaccine may be an effective strategy to prevent the outbreak of CHIKV and provide protection for travelers. In this study, we designed a multi-epitope vaccine with a 543-amino-acid structure based on the E1, E2 and capsid proteins of CHIKV, including 6 CTL epitopes, 6 HTL epitopes, 12 linear B epitopes, along with the adjuvant β-defensin III. All T-cell epitopes were docked with their corresponding MHC alleles to validate their effect on inducing immune responses, and the vaccine's sequence was proven to have acceptable physicochemical properties. Further, the developed vaccine was docked with TLR3 and TLR8, both of which play an important role in recognizing RNA viruses. Basic analyses of the docked complexes and molecular dynamic simulations revealed that the vaccine interacted strongly with TLRs. Immunological simulations indicated that the vaccine could induce both cellular and humoral immunity. Hopefully, this proposed vaccine structure can serve as a viable candidate against CHIKV infection.Communicated by Ramaswamy H. SarmaKeywords: CHIKVcapsidenvelope proteinepitope dockingmolecular dynamicsmulti-epitope vaccine AcknowledgmentsThanks to Cheng Zhao for some guidance in bioinformatics.Authors' contributionsConceptualization: F.Z. and S.M.; Methodology: F.Z.; Validation: S.M. and M.R.; Formal Analysis: P.Z., W.P., H.Y. and Y.C.; Writing—original draft preparation, S.M. and C.T.; Writing—Review and Editing: J.C.; Supervision: P.P. and J.C.; Project Administration: P.P. and J.C.; Funding acquisition: P.P.Disclosure statementThe authors report there are no competing interests to declare.Geolocation informationChangsha, Hunan province of ChinaData available statementThe data that support the findings of this study are available from the corresponding author, Pinhua Pan, upon reasonable request.Additional informationFundingThis work is supported by the National Natural Science Foundation of China (No. 81770080); the Project Program of National Clinical Research Center for Geriatric Disorders (Xiang ya Hospital, Grant No. 2020LNJJ05); National Natural Science Foundation of China (No. 8210012334); the National Key R&D Program of China (No. 2016YFC1304204).