Identification of Cross-Protective Potential Antigens against Pathogenic Brucella spp. through Combining Pan-Genome Analysis with Reverse Vaccinology. 2018

Yasmin Hisham, and Yaqoub Ashhab
Palestine-Korea Biotechnology Center, Palestine Polytechnic University, Hebron, State of Palestine.

Brucellosis is a zoonotic infectious disease caused by bacteria of the genus Brucella. Brucella melitensis, Brucella abortus, and Brucella suis are the most pathogenic species of this genus causing the majority of human and domestic animal brucellosis. There is a need to develop a safe and potent subunit vaccine to overcome the serious drawbacks of the live attenuated Brucella vaccines. The aim of this work was to discover antigen candidates conserved among the three pathogenic species. In this study, we employed a reverse vaccinology strategy to compute the core proteome of 90 completed genomes: 55 B. melitensis, 17 B. abortus, and 18 B. suis. The core proteome was analyzed by a metasubcellular localization prediction pipeline to identify surface-associated proteins. The identified proteins were thoroughly analyzed using various in silico tools to obtain the most potential protective antigens. The number of core proteins obtained from analyzing the 90 proteomes was 1939 proteins. The surface-associated proteins were 177. The number of potential antigens was 87; those with adhesion score ≥ 0.5 were considered antigen with "high potential," while those with a score of 0.4-0.5 were considered antigens with "intermediate potential." According to a cumulative score derived from protein antigenicity, density of MHC-I and MHC-II epitopes, MHC allele coverage, and B-cell epitope density scores, a final list of 34 potential antigens was obtained. Remarkably, most of the 34 proteins are associated with bacterial adhesion, invasion, evasion, and adaptation to the hostile intracellular environment of macrophages which is adjusted to deprive Brucella of required nutrients. Our results provide a manageable list of potential protective antigens for developing a potent vaccine against brucellosis. Moreover, our elaborated analysis can provide further insights into novel Brucella virulence factors. Our next step is to test some of these antigens using an appropriate antigen delivery system.

UI MeSH Term Description Entries
D002002 Brucella A genus of gram-negative, aerobic bacteria that causes BRUCELLOSIS. Its cells are nonmotile coccobacilli and are animal parasites and pathogens. The bacterium is transmissible to humans through contact with infected dairy products or tissue.
D002006 Brucellosis Infection caused by bacteria of the genus BRUCELLA mainly involving the MONONUCLEAR PHAGOCYTE SYSTEM. This condition is characterized by fever, weakness, malaise, and weight loss. Malta Fever,Undulant Fever,Brucella Infection,Brucellosis, Pulmonary,Cyprus Fever,Gibraltar Fever,Rock Fever,Brucella Infections,Brucelloses,Brucelloses, Pulmonary,Fever, Cyprus,Fever, Gibraltar,Fever, Malta,Fever, Rock,Fever, Undulant,Infection, Brucella,Pulmonary Brucelloses,Pulmonary Brucellosis
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003429 Cross Reactions Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. Cross Reaction,Reaction, Cross,Reactions, Cross
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078782 Vaccinology Branch of medicine concerned with the development of vaccines to control disease by identifying genetic and other mechanisms and pathways that determine immune responses, and thereby provide new candidate vaccine approaches.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D000942 Antigens, Bacterial Substances elaborated by bacteria that have antigenic activity. Bacterial Antigen,Bacterial Antigens,Antigen, Bacterial
D001428 Bacterial Vaccines Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease. Bacterial Vaccine,Bacterin,Vaccine, Bacterial,Vaccines, Bacterial

Related Publications

Yasmin Hisham, and Yaqoub Ashhab
February 2022, Avian pathology : journal of the W.V.P.A,
Yasmin Hisham, and Yaqoub Ashhab
January 2009, Genome dynamics,
Yasmin Hisham, and Yaqoub Ashhab
November 2015, Omics : a journal of integrative biology,
Yasmin Hisham, and Yaqoub Ashhab
November 2017, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases,
Yasmin Hisham, and Yaqoub Ashhab
January 2016, Journal of immunology research,
Copied contents to your clipboard!