Design of a new multi-epitope vaccine against Brucella based on T and B cell epitopes using bioinformatics methods.

Zhiqiang Chen,Yuejie Zhu,Tong Sha,Jianbing Ding,Fengbo Zhang,Yujiao Li,Zhiwei Li

doi:10.1017/s0950268821001229

Abstract

Brucellosis is one of the most serious and widespread zoonotic diseases, which seriously threatens human health and the national economy. This study was based on the T/B dominant epitopes of Brucella outer membrane protein 22 (Omp22), outer membrane protein 19 (Omp19) and outer membrane protein 28 (Omp28), with bioinformatics methods to design a safe and effective multi-epitope vaccine. The amino acid sequences of the proteins were found in the National Center for Biotechnology Information (NCBI) database, and the signal peptides were predicted by the SignaIP-5.0 server. The surface accessibility and hydrophilic regions of proteins were analysed with the ProtScale software and the tertiary structure model of the proteins predicted by I-TASSER software and labelled with the UCSF Chimera software. The software COBEpro, SVMTriP and BepiPred were used to predict B cell epitopes of the proteins. SYFPEITHI, RANKpep and IEDB were employed to predict T cell epitopes of the proteins. The T/B dominant epitopes of three proteins were combined with HEYGAALEREAG and GGGS linkers, and carriers sequences linked to the N- and C-terminus of the vaccine construct with the help of EAAAK linkers. Finally, the tertiary structure and physical and chemical properties of the multi-epitope vaccine construct were analysed. The allergenicity, antigenicity and solubility of the multi-epitope vaccine construct were 7.37-11.30, 0.788 and 0.866, respectively. The Ramachandran diagram of the mock vaccine construct showed 96.0% residues within the favoured and allowed range. Collectively, our results showed that this multi-epitope vaccine construct has a high-quality structure and suitable characteristics, which may provide a theoretical basis for future laboratory experiments.

Highlights

Brucella is a Gram-negative intracellular pathogen that causes brucellosis [1], it usually can be divided into 12 species in nature, including six so-called classic Brucella species, namely B. melitensis, B. abortus, B. suis, B. canis, B. ovis and B. neotomae, and six newly discovered Brucella species from wild mammals, amphibians and fish, namely B. microti, B. pinnipidialis, B. ceti, B. inopinata, B. papionis and B. vulpis
The results show that the vaccine construct has good characteristics of initiating an immunogenic response
The results showed that the confident score (C-score) of the three-dimensional (3D) model was shown as −1.52, and the template modelling (TM) score and root mean-square deviation (RMSD) of the model were 0.53 ± 0.15 and 10.4 ± 4.6 Å, respectively (Fig. 7a)

Summary

Introduction

Brucella is a Gram-negative intracellular pathogen that causes brucellosis [1], it usually can be divided into 12 species in nature, including six so-called classic Brucella species, namely B. melitensis, B. abortus, B. suis, B. canis, B. ovis and B. neotomae, and six newly discovered Brucella species from wild mammals, amphibians and fish, namely B. microti, B. pinnipidialis, B. ceti, B. inopinata, B. papionis and B. vulpis. In the genus Brucella, B. melitensis, B. abortus and B. suis have good clinical significance [2,3,4]. Clinical symptoms of human brucellosis include undulant fever, arthritis and general weakness [5, 6]. The vaccine is an ideal way to prevent Brucella infection [8]. There are no Brucella vaccines for humans, and the live-attenuated vaccines designed for animals have many defects, including interference with serological testing and human infectivity [9]. The subunit vaccine with no hidden danger and good protective effect has become a new hotspot in brucellosis research. With the rapid development of bioinformatics technology, epitopes of different antigens can be constructed as a novel vaccine with good immune effects

Methods

Results

Conclusion