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

Abstract

Enterobacter cloacae 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 Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae 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 Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.

Prediction of Putative Epitope Peptides against BaeR Associated with TCS Adaptation in Acinetobacter baumannii Using an In Silico Approach

“…The high availability of proteomic and genomic resources in a common computational in silico platform paves the way for this approach as a cost-effective measure for the prediction and selection of novel BaeR vaccine candidates. Many such studies have been conducted using an immune-informatic approach [ 19 , 20 ], and a similar study was carried out to evaluate the vaccine epitope from the GacS sensor system in A. baumannii [ 21 ].…”

“…In the context of inducing an efficient immune response, the HLA allele restriction of T-cell interaction with the selected epitopes was also computationally assessed in the present study. We selected the first five peptides that were predicted to act against MHC class I and II alleles due to having the lowest percentile ranks together with IC 50 values (<200 nm) under ANN, SMM, CombLib and NetPan scoring and ranking [ 20 ].…”

“…With the IEDB server, the location of the continuous epitopes, i.e., antigenic peptides from BaeR, was determined as an empirical rule based on parameters such as stability, hydrophilicity, exposed surface antigenic tendency, accessibility, polarity and turns. The antibody epitope predictions were evaluated based on six popular predictions [ 20 ]. In addition, the IEDB server will render an assessment on the correlation between the position of continuous epitopes and properties of polypeptide chains such as hydrophilicity, flexibility, accessibility, turns, exposed surface, polarity and antigenic propensity.…”

Designing Novel Multi-Epitope Vaccine Construct against Prevotella intermedia-Interpain A: An Immunoinformatics Approach

“…Expression and distribution of HLA alleles expressed diverse presentations between regions and ethnicity, which may impact the creation of multi-epitope-based vaccines [ 19 ]. The population coverage tool of IEDB was used to assess the CTL and HTL.…”

Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach

“…Formerly, vaccines were produced from attenuated, weakened, and dead pathogens, providing imperishable protection, but curtailing the vaccines’ swift and mass production of immunoinformatics-approach-based vaccine construct could be helpful in this regard as it involves specific antigens to the immune system to induce an adaptive immune response against bacterial infection, abating the time and cost of vaccine construction [ 9 ]. The computational-based peptide as well as mRNA vaccines have been designed against several viruses, such as COVID-19, and bacteria too [ 10 , 11 , 12 ].…”