Multi-epitope chimeric vaccine designing and novel drug targets prioritization against multi-drug resistant
Samavia Jaan1, Mohibullah Shah1, Najeeb Ullah1
1Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Abstract:
Biofilm synthesizing multi-drug resistant Staphylococcus pseudintermedius bacteria has been recognized as the human infectious agent. It has been detected in the diseases of skin, ear, and postoperative infections. Its infections are becoming a major health problem due to its multi-drug resistance capabilities. However, no commercial vaccine for the treatment of its infections is currently available in the market. Here we employed the subtractive proteomics and reverse vaccinology approach to determine the potential novel drug and vaccine targets against S. pseudintermedius infections in humans. After screening the core-proteome of the 39 complete genomes of S. pseudintermedius, 2 metabolic pathways dependent and 34 independent proteins were determined as novel potential drug targets. Two proteins were found and used as potential candidates for designing the chimeric vaccine constructs. Depending on the properties such as antigenicity, toxicity and solubility, multi-epitope based vaccines constructs were designed. For immunogenicity enhancement, different specific sequences like linkers, PADRE sequences and molecular adjuvants were added. Molecular docking and molecular dynamic simulation analyses were performed to evaluate the prioritized vaccine construct's interactions with human immune cells HLA and TLR4. Finally, the cloning and expression ability of the vaccine construct was determined in the bacterial cloning system and human body immune response was predicted through immune simulation analysis. In conclusion, this study proposed the potential drug and vaccine targets and also designed a chimera vaccine to be tested and validated against infectious S. pseudintermedius species.
Insights
Multi-drug resistant Staphylococcus pseudintermedius infections pose a significant threat. This study identifies novel drug and vaccine targets, designing a potential chimeric vaccine against these challenging bacterial infections.
Area of Science:
- Microbiology
- Immunology
- Bioinformatics
Background:
- Biofilm-producing, multi-drug resistant *Staphylococcus pseudintermedius* is an emerging human pathogen causing skin, ear, and postoperative infections.
- The increasing prevalence of antibiotic resistance in *S. pseudintermedius* infections highlights the urgent need for novel therapeutic strategies, as no commercial vaccine is currently available.
- Addressing the challenge of *S. pseudintermedius* infections requires innovative approaches due to its multi-drug resistance.
Purpose of the Study:
- To identify novel drug and vaccine targets against *Staphylococcus pseudintermedius* infections using subtractive proteomics and reverse vaccinology.
- To design and evaluate potential multi-epitope chimeric vaccine constructs against *S. pseudintermedius*.
Main Methods:
- Subtractive proteomics and reverse vaccinology were employed to screen core proteomes from 39 *S. pseudintermedius* genomes.
- Potential drug targets (36 proteins) and vaccine candidates (2 proteins) were identified. Multi-epitope vaccine constructs were designed incorporating antigenicity, toxicity, solubility, linkers, PADRE sequences, and molecular adjuvants.
- In silico analyses including molecular docking, molecular dynamic simulations, and immune simulations were performed to assess vaccine construct efficacy and immunogenicity.
Main Results:
- Thirty-six novel potential drug targets, including 2 metabolic pathway-dependent and 34 independent proteins, were identified.
- Two proteins were selected as candidates for chimeric vaccine design, leading to the development of multi-epitope constructs with enhanced immunogenicity.
- In silico evaluations demonstrated favorable interactions of the prioritized vaccine construct with human immune receptors (HLA and TLR4) and predicted effective immune responses.
Conclusions:
- This study successfully identified potential drug and vaccine targets against *Staphylococcus pseudintermedius*.
- A chimeric vaccine construct was designed, showing promise for further experimental validation against *S. pseudintermedius* infections.
- The findings provide a foundation for developing new therapeutic and prophylactic strategies against multi-drug resistant *S. pseudintermedius*.
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