Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes nosocomial infection with a high mortality rate in immunocompromised individuals. With the frequent emergence of multidrug-resistant A. baumannii strains that have rapidly gained resistance to most antibiotics, an extensive search for an effective A. baumannii vaccine is ongoing. Over the decade, many subunit vaccine candidates were identified using reverse vaccinology and in vivo animal studies for validation. Nineteen subunit vaccine candidates with a wide range of efficacy, from 14% to 100% preclinical survival rates, were included in this review. This article provides an updated review of several outer membrane proteins (Omp) that emerged as vaccine candidates with great potential, including OmpA, Omp34, Omp22 and BamA, based on their high conservancy, antigenicity, and immune protection against A. baumannii infection. However, there is still no licenced A. baumannii vaccine currently due to several practical issues that have yet to be resolved, such as inconsistencies between validation studies, antigen variability and insolubility. Moving forward, much investigation and innovation are still required to tackle these challenges for the regulatory approval of an A. baumannii subunit vaccine, including standardisation of immunisation study parameters, improving antigen solubility and the incorporation of nucleic acid vaccine technology.

Frontiers in Immunology

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

Review

作者: Tan, Yong Chiang ; Lahiri, Chandrajit

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.

Pathogens4区 · 医学

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

4区 · 医学

ReviewOA

作者: Morici, Lisa A. ; Gellings, Patrick S. ; Wilkins, Ashley A.

Acinetobacter baumannii has been a major cause of nosocomial infections for decades. The absence of an available vaccine coupled with emerging multidrug resistance has prevented the medical community from effectively controlling this human pathogen. Furthermore, the ongoing pandemic caused by SARS-CoV-2 has increased the risk of hospitalized patients developing ventilator-associated pneumonia caused by bacterial opportunists including A. baumannii. The shortage of antibiotics in the development pipeline prompted the World Health Organization to designate A. baumannii a top priority for the development of new medical countermeasures, such as a vaccine. There are a number of important considerations associated with the development of an A. baumannii vaccine, including strain characteristics, diverse disease manifestations, and target population. In the past decade, research efforts have revealed a number of promising new immunization strategies that could culminate in a safe and protective vaccine against A. baumannii. In this review, we highlight the recent progress in the development of A. baumannii vaccines, discuss potential challenges, and propose future directions to achieve an effective intervention against this human pathogen.

100 项与 VXD-001 相关的药物交易

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