Immunoinformatics Approach to Design a Novel Epitope-Based Oral Vaccine Against Helicobacter pylori

被引:45
作者
Hugo Urrutia-Baca, Victor [1 ]
Gomez-Flores, Ricardo [1 ]
Angelica De La Garza-Ramos, Myriam [2 ]
Tamez-Guerra, Patricia [1 ]
Guadalupe Lucio-Sauceda, Daniela [1 ]
Cristina Rodriguez-Padilla, Maria [1 ]
机构
[1] Autonomous Univ Nuevo Leon, Sch Biol Sci, Lab Immunol & Virol, Pedro Alba & Manuel L Barraga St, Monterrey 66450, NL, Mexico
[2] Autonomous Univ Nuevo Leon, Ctr Res & Dev Hlth Sci, Integral Dent Unit & Specialties, Monterrey, Mexico
关键词
Helicobacter pylori; in silico; multiepitope; oral vaccine; reverse vaccinology; MENINGOCOCCAL SEROGROUP-B; PROTEIN-STRUCTURE; PREDICTION; WEB; IMMUNOGENICITY; RECOMBINANT; DATABASE; SAFETY; 4CMENB; MODEL;
D O I
10.1089/cmb.2019.0062
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Helicobacter pylori is an infectious agent that colonizes the gastric mucosa of half of the population worldwide. This bacterium has been recognized as belonging to group 1 carcinogen by the World Health Organization for the role in development of gastritis, peptic ulcers, and cancer. Due to the increase in resistance to antibiotics used in the anti-H. pylori therapy, the development of an effective vaccine is an alternative of great interest, which remains a challenge. Therefore, a rational, strategic, and efficient vaccine design against H. pylori is necessary where the use of the most current bioinformatics tools could help achieve it. In this study, immunoinformatics approach was used to design a novel multiepitope oral vaccine against H. pylori. Our multiepitope vaccine is composed of cholera toxin subunit B (CTB) that is used as a mucosal adjuvant to enhance vaccine immunogenicity for oral immunization. CTB fused to 11 epitopes predicted of pathogenic (UreB(170-189), VacA(459-478), CagA(1103-1122), GGT(106-126), NapA(30-44), and OipA(211-230)) and colonization (HpaA(33-52), FlaA(487-506), FecA(437-456), BabA(129-149), and SabA(540-559)) proteins from H. pylori. CKS9 peptide (CKSTHPLSC) targets epithelial microfold cells to enhance vaccine uptake from the gut barrier. All sequences were joined to each other by proper linkers. The vaccine was modeled and validated to achieve a high-quality three-dimensional structure. The vaccine design was evaluated as nonallergenic, antigenic, soluble, and with an appropriate molecular weight and isoelectric point. Our results suggest that our newly designed vaccine could serve as a promising anti-H. pylori vaccine candidate.
引用
收藏
页码:1177 / 1190
页数:14
相关论文
共 49 条
[1]   Gapped sequence alignment using artificial neural networks: application to the MHC class I system [J].
Andreatta, Massimo ;
Nielsen, Morten .
BIOINFORMATICS, 2016, 32 (04) :511-517
[2]  
[Anonymous], 1994, IARC Monogr Eval Carcinog Risks Hum, V61, P1
[3]   Cholera Toxin B: One Subunit with Many Pharmaceutical Applications [J].
Baldauf, Keegan J. ;
Royal, Joshua M. ;
Hamorsky, Krystal Teasley ;
Matoba, Nobuyuki .
TOXINS, 2015, 7 (03) :974-996
[4]   Epidemiology of Helicobacter pylori infection [J].
Burucoa, Christophe ;
Axon, Anthony .
HELICOBACTER, 2017, 22
[5]   OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines [J].
Chen, Wei-Hua ;
Lu, Guanting ;
Chen, Xiao ;
Zhao, Xing-Ming ;
Bork, Peer .
NUCLEIC ACIDS RESEARCH, 2017, 45 (D1) :D940-D944
[6]   Codon Optimization OnLine (COOL): a web-based multi-objective optimization platform for synthetic gene design [J].
Chin, Ju Xin ;
Chung, Bevan Kai-Sheng ;
Lee, Dong-Yup .
BIOINFORMATICS, 2014, 30 (15) :2210-2212
[7]   VERIFICATION OF PROTEIN STRUCTURES - PATTERNS OF NONBONDED ATOMIC INTERACTIONS [J].
COLOVOS, C ;
YEATES, TO .
PROTEIN SCIENCE, 1993, 2 (09) :1511-1519
[8]   Secretome, surfome and immunome: emerging approaches for the discovery of new vaccine candidates against bacterial infections [J].
Dwivedi, Pratistha ;
Alam, Syed Imteyaz ;
Tomar, Rajesh Singh .
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY, 2016, 32 (09)
[9]   Vaccine design: emerging concepts and renewed optimism [J].
Grimm, Sebastian K. ;
Ackerman, Margaret E. .
CURRENT OPINION IN BIOTECHNOLOGY, 2013, 24 (06) :1078-1088
[10]   Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils [J].
Guo, Le ;
Yang, Hua ;
Tang, Feng ;
Yin, Runting ;
Liu, Hongpeng ;
Gong, Xiaojuan ;
Wei, Jun ;
Zhang, Ying ;
Xu, Guangxian ;
Liu, Kunmei .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2017, 7