In-Silico Vaccine Design Based on a Novel Vaccine Candidate Against Infections Caused by Acinetobacter baumannii

Acinetobacter baumannii is notorious for causing serious infections of the skin, lungs, soft tissues, bloodstream, and urinary tract. Despite the overwhelming information available so far, there has still been no approved vaccine in the market to prevent these infections. Therefore, this study focuses on developing a rational vaccine design using the technique of epitope mapping to curb the infections caused by A. baumannii. An outer membrane protein with immunogenic potential as well as all the properties of a good vaccine candidate was selected and used to calculate epitopes for selection on the basis of a low percentile rank, high binding scores, good immunological properties, and non-allergenicity. Thus, a 240 amino-acid vaccine sequence was obtained by manually joining all the epitopes in sequence-wise manner with the appropriate linkers, namely AAY, GPGPG, and EAAAK. Additionally, a 50S ribosomal protein L7/L12, agonist to the human innate immune receptors was attached to the N-terminus to increase the overall immune response towards the vaccine. As a result, enhanced overall protein stability, expression, immunostimulatory capabilities, and solubility of the designed construct were observed. Molecular dynamic simulations revealed the compactness and stability of the polypeptide construct. Moreover, molecular docking exhibited strong binding of the designed vaccine with TLR-4 and TLR-9. In-silico immune simulations indicated an immense increment in T-cell and B-cell populations. Bioinformatic tools also significantly assisted with optimizing codons which allowed for successful cloning of constructs into desired host vectors. Using in-silico tools to design a vaccine against A. baumannii demonstrated that this construct could pave the way for successfully combating infections caused by multidrug-resistant bacteria.

Automated summary

This study focuses on developing a rational vaccine design against Acinetobacter baumannii using epitope mapping technique. By selecting an outer membrane protein with immunogenic potential, epitopes were calculated for selection based on certain criteria. A vaccine sequence of 240 amino acids was obtained by joining all the epitopes in a sequence-wise manner and adding a protein agonist to human innate immune receptors. The designed construct showed enhanced overall protein stability, expression, immunostimulatory capabilities, and solubility. Molecular dynamics simulations and molecular docking demonstrated the compactness, stability, and strong binding of the vaccine with Toll-like receptors. In-silico immune simulations indicated a significant increase in T-cell and B-cell populations. Bioinformatic tools were also useful in optimizing codons for successful cloning of constructs into host vectors.