Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

Abstract

In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.

Global Risk Maps of Climate Change Impacts on the Distribution of Acinetobacter baumannii Using GIS

“…Because most A. baumannii strains are multidrug-resistant, the use of multiple antibiotics often is still not sufficient to treat infection, and for this reason, it has been suggested that new therapies and more well-controlled studies are needed to study possible treatment options, as well as placing a greater emphasis on the prevention of infection transmission [ 13 ]. In line with this vision, the World Health Organization has declared A. baumannii a top priority for the development of new medical countermeasures, such as a vaccine, [ 64 ] and work toward such a vaccine is indeed underway, [ 65 ] although no vaccine has been developed sufficiently to the point of human clinical trials to date [ 66 ].…”

A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins

“…In a reverse vaccinology study, a dataset of A. baumannii whole genomes investigated to identify the new putative vaccine candidates and selected DcaP-like protein and HP-2 as candidates among 11 ( 41 ). Overall, there are many different approaches to investigate the vaccine candidates both immunoinformatic and other omics strategies, which are extensively reviewed ( 42 ).…”

The Prevalence of Multidrug-Resistant Acinetobacter baumannii and Its Vaccination Status among Healthcare Providers

“…Most studies have focused on traditional methods and platforms, such as subunit and killed vaccines. However, there are ongoing explorations of novel antigen transporters and enhanced delivery mechanisms, including nucleic acid vaccines, virus vectors, conjugated carriers, and co-delivery [ 21 , 113 , 117 ]. It is worth noting that mRNA and DNA vaccine technologies have gained significant recognition due to the competition surrounding COVID-19 vaccines.…”

“…Before advancing to clinical trials, vaccine candidates must undergo testing in experimental animals to assess reactogenicity and immune response [ 20 ]. Furthermore, it is essential to evaluate the pharmacological and toxicological properties of the targeted vaccine candidates to ensure their safety and efficacy [ 21 ]. This review investigates the spread of multidrug-resistant A. baumannii infections in healthcare settings in Saudi Arabia and explores potential measures to prevent their transmission.…”