A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens

Abstract

Serratia marcescens is now an important opportunistic pathogen that can cause serious infections in hospitalized or immunocompromised patients. Here, we used extensive bioinformatic analyses based on reverse vaccinology and subtractive proteomics-based approach to predict potential vaccine candidates against S. marcescens. We analyzed the complete proteome sequence of 49 isolate of Serratia marcescens and identified 5 that were conserved proteins, non-homologous from human and gut flora, extracellular or exported to the outer membrane, and antigenic. The identified proteins were used to select 5 CTL, 12 HTL, and 12 BCL epitopes antigenic, non-allergenic, conserved, hydrophilic, and non-toxic. In addition, HTL epitopes were able to induce interferon-gamma immune response. The selected peptides were used to design 4 multi-epitope vaccines constructs (SMV1, SMV2, SMV3 and SMV4) with immune-modulating adjuvants, PADRE sequence, and linkers. Peptide cleavage analysis showed that antigen vaccines are processed and presented via of MHC class molecule. Several physiochemical and immunological analyses revealed that all multiepitope vaccines were non-allergenic, stable, hydrophilic, and soluble and induced the immunity with high antigenicity. The secondary structure analysis revealed the designed vaccines contain mainly coil structure and alpha helix structures. 3D analyses showed high-quality structure. Molecular docking analyses revealed SMV4 as the best vaccine construct among the four constructed vaccines, demonstrating high affinity with the immune receptor. Molecular dynamics simulation confirmed the low deformability and stability of the vaccine candidate. Discontinuous epitope residues analyses of SMV4 revealed that they are flexible and can interact with antibodies. In silico immune simulation indicated that the designed SMV4 vaccine triggers an effective immune response. In silico codon optimization and cloning in expression vector indicate that SMV4 vaccine can be efficiently expressed in E. coli system. Overall, we showed that SMV4 multi-epitope vaccine successfully elicited antigen-specific humoral and cellular immune responses and may be a potential vaccine candidate against S. marcescens. Further experimental validations could confirm its exact efficacy, the safety and immunogenicity profile. Our findings bring a valuable addition to the development of new strategies to prevent and control the spread of multidrug-resistant Gram-negative bacteria with high clinical relevance.

Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma

“…Higher processing scores denote enhanced antigen processing outcomes [75,76]. Given IFN-γ's pivotal role in acquired and innate immunity against tumors [77], we proceeded to assess the IFN-γ inducing HTL epitopes. All chosen epitopes were proficient in inducing IFN-γ.…”

“…All chosen epitopes were proficient in inducing IFN-γ. Due to the importance of HLA specificity in T-cell epitope selection [77], we employed molecular docking simulations to establish the connections between these epitopes and their respective HLA alleles. The analyses revealed robust binding in the epitope-MHC complexes, evident from their higher global energy scores.…”

De novo identification of bacterial antigens of a clinical isolate by combining use of proteosurfaceomics, secretomics, and BacScan technologies

“…Bacterial infectious diseases pose a serious threat to public health and cause huge economic losses worldwide ( 1 , 2 ). While vaccines are widely recognized as the most effective countermeasure to prevent bacterial infections ( 3 , 4 ), developing effective bacterial vaccines remains a significant challenge due to the presence of multiple serotypes and complex genomes. As demonstrated by methicillin-resistant Staphylococcus aureus , emerging bacterial epidemics pose a significant threat to human and animal populations ( 5 ).…”

“…Although the traditional inactivated whole-pathogen vaccines may be effective against homologous strains, they are often associated with local or systemic side effects ( 6 ). In contrast, subunit vaccines, which consist of antigenic components of the pathogen rather than the entire pathogen ( 3 ), are much safer and represent the next-generation of vaccines.…”