Immunoinformatics-driven multi-epitope vaccine design as a promising strategy against multidrug-resistant pathogens:...

Infections caused by multidrug-resistant (MDR) pathogens, both gram-negative and gram-positive organisms, have transformed into a silent global pandemic. These pathogens, especially ESKAPE pathogens, exhibit wide resistance patterns to several clinically significant antibiotics. This has decreased the effectiveness of already available antibiotics, increasing mortality, morbidity, economic burden and prolonged hospital stay. As the discovery of new antibiotics is an extensive and time-consuming process, an urgent need for innovative and practical preventive strategies arises. This review emphasizes the need, advancement and practicality of immunoinformatic tools and in silico vaccine designing and development against MDR pathogens. Research shows that MDR pathogens demonstrate a variety of resistance pathways, including target alteration, enzymatic degradation and efflux pumps, to tolerate therapeutically available antibiotics. The notable benefits of in silico vaccine designing include rapid identification of conserved antigens, even in variable pathogens, epitope prediction with antigenic potential, population coverage across various populations, less time, cost and improved precision in creating a multi-epitope vaccine against these MDR pathogens. Moreover, molecular docking, molecular dynamic simulations, immune simulations and expression analysis assist in predicting the molecular behavior of the designed vaccine. The increasing prevalence of MDR infections emphasizes the critical need for prevention measures rather than conventional therapy options. Use of immunoinformatics and in silico approaches presents a potent, efficient and cost-effective method to design and create multi-epitope vaccines against MDR pathogens. However, limitations such as false positives, reproducibility concerns with varying software and potential bias due to the use of curated databases in reverse vaccinology may pose a challenge. Incorporation of in silico vaccine development in future research can play a pivotal role in combating antimicrobial resistance and improving health outcomes globally.