Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

Abstract

Brucella suis mediates the transmission of brucellosis in humans and animals and a significant facultative zoonotic pathogen found in livestock. It has the capacity to survive and multiply in a phagocytic environment and to acquire resistance under hostile conditions thus becoming a threat globally. Antibiotic resistance is posing a substantial public health threat, hence there is an unmet and urgent clinical need for immune-based non-antibiotic methods to treat brucellosis. Hence, we aimed to explore the whole proteome of Brucella suis to predict antigenic proteins as a vaccine target and designed a novel chimeric vaccine (multi-epitope vaccine) through subtractive genomics-based reverse vaccinology approaches. The applied subsequent hierarchical shortlisting resulted in the identification of Multidrug efflux Resistance-nodulation-division (RND) transporter outer membrane subunit (gene BepC) that may act as a potential vaccine target. T-cell and B-cell epitopes have been predicted from target proteins using a number of immunoinformatic methods. Six MHC I, ten MHC II, and four B-cell epitopes were used to create a 324-amino-acid MEV construct, which was coupled with appropriate linkers and adjuvant. To boost the immunological response to the vaccine, the vaccine was combined with the TLR4 agonist HBHA protein. The MEV structure predicted was found to be highly antigenic, non-toxic, non-allergenic, flexible, stable, and soluble. To confirm the interactions with the receptors, a molecular docking simulation of the MEV was done using the human TLR4 (toll-like receptor 4) and HLAs. The stability and binding of the MEV-docked complexes with TLR4 were assessed using molecular dynamics (MD) simulation. Finally, MEV was reverse translated, its cDNA structure was evaluated, and then, in silico cloning into an E. coli expression host was conducted to promote maximum vaccine protein production with appropriate post-translational modifications. These comprehensive computer calculations backed up the efficacy of the suggested MEV in protecting against B. suis infections. However, more experimental validations are needed to adequately assess the vaccine candidate's potential. Highlights• Subtractive genomic analysis and reverse vaccinology for the prioritization of novel vaccine target • Examination of chimeric vaccine in terms of allergenicity, antigenicity, MHC I, II binding efficacy, and structural-based studies • Molecular docking simulation method to rank based vaccine candidate and understand their binding modes

In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis

“…Adjuvants are important components of vaccines that can boost innate and adaptive immune responses [99] . Many proteins from M. tuberculosis have adjuvant properties and have been used to design vaccine [17] , [27] , [87] , [100] , [101] , [102] , [103] , [104] , [105] . One of the most widely used is HBHA [100] , [101] , [102] , [103] , [104] , [105] , which is a potent immunostimulant that induces dendritic cells (DCs) maturation through TLR4 processing [105] , [106] .…”

“…Many proteins from M. tuberculosis have adjuvant properties and have been used to design vaccine [17] , [27] , [87] , [100] , [101] , [102] , [103] , [104] , [105] . One of the most widely used is HBHA [100] , [101] , [102] , [103] , [104] , [105] , which is a potent immunostimulant that induces dendritic cells (DCs) maturation through TLR4 processing [105] , [106] . DCs treated with HBHA have been found to activate naive T cells, polarize CD4 + and CD8 + T cells to secrete IFN-γ, and induce T-cell-mediated cytotoxicity [47] .…”

Brucella infection and Toll-like receptors

“…The modified LPS with a defective core purified from Brucella carrying a mutated wadC gene potentiated cytokine secretion, representing a potential for vaccine development ( Conde-Álvarez et al., 2012 ; Conde-Álvarez et al., 2013 ; Zhao et al., 2018 ). Based on the TLR4, some groups design the multi-epitope vaccine candidates against Brucella ( Li, M. et al., 2022 ; Tarrahimofrad et al., 2022 ; Jalal et al., 2023 ; Malik et al., 2023 ; Yin et al., 2023 ). B. abortus Omp16 lipoprotein would be able to induce a protective immune response via a TLR4-dependent manner and is a promising self-adjuvanting vaccine against brucellosis ( Pasquevich et al., 2010 ).…”

A comprehensive approach to developing a multi-epitope vaccine against Mycobacterium tuberculosis: from in silico design to in vitro immunization evaluation

“…Accurate recognition of vaccines by antigen-presenting cells (APCs) and their efficient presentation to adaptive immune cells is critical to activating immune responses. Therefore, MHC I/II binding score, immunogenicity, antigenicity, and IFN-g inducing ability are key components that require optimal screening during the screening process of immunodominant epitopes (48)(49)(50). Herein, to ensure the PP13138R vaccine's accuracy and effectiveness, we employed a rigorous evaluation process that involved analyzing the vaccine's structure and properties, including the construction of the secondary, tertiary, tertiary structure, and recombinant plasmid.…”