Structure prediction and immune simulation of Brucella Omp2a-BtpB multi-epitope vaccine
LI Min1 ZHU Yuejie2 HU Jinwei1 GU Ting1 YU Mingkai3 CHEN Zhiqiang3 DING Jianbing3 ZHANG Fengbo1#br#
1.Medical Laboratory Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China; 2.Reproductive Pregnancy Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China; 3.Department of Immunology, Basic Medical College, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China
Abstract Objective To predict and analyze T and B cell dominant epitopes of Omp2a and BtpB of Brucella by bioinformatics and construct a novel multi-epitope vaccine. Methods The amino acid sequences of the proteins, which were obtained from UniProt Database. Furthermore, the 3D structure of the proteins was builded by I-TASSER. Then being selected dominant epitopes and adjuvants to construct an multi-epitope vaccine and perform immune simulation. Results Two B cell dominant epitopes, five CTL cell dominant epitopes and three Th cell dominant epitopes were obtained in Omp2a. One B cell dominant epitope, five CTL cell dominant epitopes and one Th cell dominant epitope were obtained in BtpB. The constructed multi-epitope vaccine was a hydrophilic stable protein. Conclusion A novel Brucella multi-epitope vaccine is designed by using a bioinformatics approach, providing a theoretical basis for further research on Brucella vaccines.
[1] Jiang H，O’Callaghan D，Ding JB. Brucellosis in China：history，progress and challenge [J]. Infect Dis Poverty，2020，9（3）：101-104.
[2] De Groot AS，Moise L，Terry F，et al. Better epitope discovery，precision immune engineering，and accelerated vaccine design using immunoinformatics tools [J]. Front Immunol，2020，11：442.
[3] 陈志强，沙桐，李智伟，等.布鲁氏菌Omp25蛋白抗原表位的生物信息学分析[J].新疆医科大学学报，2020，43（4）：414-418.
[4] Zhang F，Li Z，Jia B，et al. The immunogenicity of OMP31 peptides and its protection against brucella melitensis infection in mice [J]. Sci Rep，2019，9（1）：3512.
[5] Sha T，Li Z，Zhang C，et al. Bioinformatics analysis of candidate proteins Omp2b，P39 and BLS for Brucella multivalent epitope vaccines [J]. Microb Pathog，2020，147：104318.
[6] 杨妍，朱玥洁，胡金伟，等.布鲁氏菌Omp10蛋白抗原表位的生物信息学分析[J].新疆医科大学学报，2016，39（10）：1261-1266.
[7] Avila-Calderón ED，Lopez-Merino A，Jain N，et al. Characterization of outer membrane vesicles from Brucella melitensis and protection induced in mice [J]. Clin Dev Immunol，2012，2012：352493.
[8] Cloeckaert A，Vergnaud G，Zygmunt MS. Omp2b porin alteration in the course of evolution of brucella spp [J].Front Microbiol，2020，11：284.
[9] Pathak P，Kumar A，Thavaselvam D. Evaluation of recombinant porin （rOmp2a) protein as a potential antigen candidate for serodiagnosis of Human Brucellosis [J]. BMC Infect Dis，2017，17（1）：485.
[10] G?覥owacka P，■akowska D，Naylor K，et al. Brucella-virulence factors，pathogenesis and treatment [J]. Pol J Microbiol，2018，67（2）：151-161.
[11] Xiang Z，He Y. Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology [J]. BMC Bioinformatics，2013，14（Suppl 4）：S2.
[12] Yang J，Zhang Y. I-TASSER server：new development for protein structure and function predictions [J]. Nucleic Acids Res，2015，43（W1）：W174-W181.
[13] Zhang C，Freddolino PL，Zhang Y. COFACTOR：improved protein function prediction by combining structure，sequence and protein-protein interaction information [J]. Nucleic Acids Res，2017，45（W1）：W291-W299.
[14] Wiederstein M，Sippl MJ. ProSA-web：interactive web service for the recognition of errors in three-dimensional structures of proteins [J]. Nucleic Acids Res，2007，35（Web Server issue)：W407-W410.
[15] Sippl MJ. Recognition of errors in three-dimensional structures of proteins [J]. Proteins，1993，17（4)：355-362.
[16] Larsen JE，Lund O，Nielsen M. Improved method for predicting linear B-cell epitopes [J]. Immunome Res，2006， 2：2.
[17] Solanki V，Tiwari V. Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii [J]. Sci Rep，2018，8（1）：9044.
[18] Rapin N，Lund O，Bernaschi M，et al. Computational immunology meets bioinformatics： the use of prediction tools for molecular binding in the simulation of the immune system [J]. PLoS One，2010，5（4）：e9862.
[19] Chand Y，Singh S. Prioritization of potential vaccine candidates and designing a multiepitope-based subunit vaccine against multidrug-resistant Salmonella Typhi str. CT18：a subtractive proteomics and immunoinformatics approach [J]. Microb Pathog，2021，159：105150.
[20] Zhou K，Wu B，Pan H，et al. ONE health approach to address zoonotic brucellosis：a spatiotemporal associations study between animals and humans [J]. Front Vet Sci，2020，7：521.
[21] Zheng R，Xie S，Lu X，et al. A systematic review and meta-analysis of epidemiology and clinical manifestations of human brucellosis in China [J]. Biomed Res Int，2018， 2018：5712920.
[22] Salcedo SP，Marchesini MI，Degos C，et al. BtpB，a novel Brucella TIR-containing effector protein with immune modulatory functions [J]. Front Cell Infect Microbiol，2013，3：28.
[23] Chen Z，Zhu Y，Sha T，et al. Design of a new multi-epitope vaccine against Brucella based on T and B cell epitopes using bioinformatics methods [J]. Epidemiol Infect，2021，149：e136.
[24] Zhou C，Xu M，Xiao Z，et al. Distribution of HLA-DQA1，-DQB1 and -DRB1 genes and haplotypes in Han，Uyghur，Kazakh and Hui populations inhabiting Xinjiang Uyghur Autonomous Region，China [J]. Int J Immunogenet，2021，48（3）：229-238.
[25] Yu M，Zhu Y，Li Y，et al. Design of a novel multi-epitope vaccine against echinococcus granulosus in immunoinformatics [J]. Front Immunol，2021，12：668492.
