Screening of potential vaccine candidates against pathogenic Brucella spp. using compositive reverse vaccinology

Abstract

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.

Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines

“…Among them, the clusters for “translation, ribosomal structure and biogenesis” (184, 10.8%), “replication, recombination and repair” (158, 9.2%) and “amino acid transport and metabolism” (153, 9.0%) were the top three largest functional groups ( Figure 1B ). Then, the 95 proteins that carried one or more protective signatures recurring in known bacterial protective antigens ( Altindis et al., 2015 ) were further analyzed using two reverse vaccinology tools, including the self-developed Multifactor Prediction of Protective Antigens (MPPA) platform based on subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability ( Zai et al., 2021 ) and the Vax-ELAN pipeline based on subcellular localization, transmembrane helix prediction, adhesion property, non-homology with host proteins, etc ( Rawal et al., 2021 ) ( Figure 1C ). The potential immunogenic antigens—Tul4, OmpA, FopA, and DnaK—had both a high MPPA score and Vax-ELAN value, indicating likely involvement in antigenicity and virulence, and were further assessed as vaccine candidates.…”

Recent Advances in Genomics-Based Approaches for the Development of Intracellular Bacterial Pathogen Vaccines

“…The inclusion of PE_PGRS49 in existing BCG vaccines may enhance their efficacy [ 106 ]. Recently, the RV strategy was successfully applied to many other intracellular bacterial pathogens for vaccine development, including Brucella spp., C. pneumoniae , R. prowazekii , Anaplasma spp., Ehrlichia spp., S. pyogenes , etc., [ 25 , 103 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ].…”

Novel antigenic proteins of Mycoplasma synoviae as potential vaccine candidates

“…Similar approaches have been widely used for the discovery of new vaccine development in infectious diseases 15,16 .…”