Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification

• Published in: Microorganisms (Basel) Vol. 10; no. 8; p. 1621
• Main Authors: Naveed, Muhammad, Jabeen, Khizra, Naz, Rubina, Mughal, Muhammad Saad, Rabaan, Ali A, Bakhrebah, Muhammed A, Alhoshani, Fahad M, Aljeldah, Mohammed, Shammari, Basim R Al, Alissa, Mohammed, Sabour, Amal A, Alaeq, Rana A, Alshiekheid, Maha A, Garout, Mohammed, Almogbel, Mohammed S, Halwani, Muhammad A, Turkistani, Safaa A, Ahmed, Naveed
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.08.2022; MDPI
• Subjects: AMR; antibiotic resistance; bioinformatics; Computer applications; Cytoplasm; Design modifications; DNA methylation; Dynamic stability; Enterobacter cloacae; Epigenetics; Epitopes; Immune response; Immune system; immunoinformatic; Immunology; in silico; Infections; Kinases; Lymphocytes; Major histocompatibility complex; Molecular docking; mRNA vaccines; Performance prediction; Proteins; Respiratory tract; Respiratory tract diseases; Sepsis; TLR4 protein; Toll-like receptors; Urethritis; Vaccination; Vaccines; immunoinformatic; in silico; antibiotic resistance; AMR; bioinformatics
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms10081621

is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of were used to predict the epitopes for the construction of an mRNA vaccine against infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.