OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections

Huang, Weiwei; Wang, Shijie; Yao, Yufeng; Xia, Ye; Xu, Yang; Long, Quan; Sun, Wenjun; Liu, Cunbao; Li, Yang; Ma, Yanbing

doi:10.1016/j.vaccine.2015.07.031

Cited by 54 publications

(42 citation statements)

References 31 publications

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“…Indeed, passive transfer of polyclonal anti-OmpA, anti-OmpW, or anti-NucAb immune serum from vaccinated mice transferred protection to recipient mice, validating the approach (300,301,303). In other experiments, antibodies against the outer membrane transporters and polysaccharides were able to facilitate opsonization and subsequent phagocytosis of A. baumannii leading to decreased tissue loads (304).…”

Section: Active and Passive Vaccinationmentioning

confidence: 78%

“…The vaccine markedly reduced bacterial burden, although its improvement of survival was less impressive. Other outer membrane proteins, such as OmpW, have also been reported to be effective vaccines (302,303). However, a challenge of any active vaccine for Acinetobacter is to define a patient population that is of sufficiently high short-term risk of infection to make efficacy definable in a reasonably sized clinical trial, while still allowing sufficient time for the at-risk patient to generate protective immunity to an active vaccine before infection begins.…”

Section: Active and Passive Vaccinationmentioning

confidence: 99%

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Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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Section: Active and Passive Vaccinationmentioning

confidence: 78%

Section: Active and Passive Vaccinationmentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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“…It was reported that subunit proteins of A. baumannii, including iron-regulated outer membrane proteins (IROMP)25, biofilm-associated protein (Bap)26, poly-N-acetyl-β-(1–6)-glucosamine (PNAG)27, trimeric autotransporter protein (Ata)28, outer membrane protein A (OmpA)29, and outer membrane protein W (OmpW)30, were potent vaccine candidates and provided effective immune protection against A. baumannii infection in animal models. We previously identified another antigenic outer membrane protein, Omp22, that could also provide immune protection against lethal challenge with clonally distinct clinical A. baumannii isolates in a murine sepsis model24.…”

Section: Discussionmentioning

confidence: 99%

Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection

Huang

Wang

Yao

et al. 2016

Sci Rep

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Outer membrane vesicles (OMVs) have proven to be highly immunogenic and induced an immune response against bacterial infection in human clinics and animal models. We sought to investigate whether engineered OMVs can be a feasible antigen-delivery platform for efficiently inducing specific antibody responses. In this study, Omp22 (an outer membrane protein of A. baumannii) was displayed on E. coli DH5α-derived OMVs (Omp22-OMVs) using recombinant gene technology. The morphological features of Omp22-OMVs were similar to those of wild-type OMVs (wtOMVs). Immunization with Omp22-OMVs induced high titers of Omp22-specific antibodies. In a murine sepsis model, Omp22-OMV immunization significantly protected mice from lethal challenge with a clinically isolated A. baumannii strain, which was evidenced by the increased survival rate of the mice, the reduced bacterial burdens in the lung, spleen, liver, kidney, and blood, and the suppressed serum levels of inflammatory cytokines. In vitro opsonophagocytosis assays showed that antiserum collected from Omp22-OMV-immunized mice had bactericidal activity against clinical isolates, which was partly specific antibody-dependent. These results strongly indicated that engineered OMVs could display a whole heterologous protein (~22 kDa) on the surface and effectively induce specific antibody responses, and thus OMVs have the potential to be a feasible vaccine platform.

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“…Although the vast majority of patients who become infected with Acinetobacter spp. are immunocompromised, which complicates intervention strategies, vaccines have been proposed as an alternative method to fight MDR Acinetobacter (108,109), and several promising candidates have been described (107,(110)(111)(112)(113)(114). Individuals for whom immunocompromise could potentially be predicted a priori, such as patients undergoing cancer treatments or surgery and military personnel entering conflicts, may benefit from a prophylactic vaccination strategy (115).…”

Section: Future Directionsmentioning

confidence: 99%

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2016

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The genus Acinetobacter encompasses multiple nosocomial opportunistic pathogens that are of increasing worldwide relevance because of their ability to survive exposure to various antimicrobial and sterilization agents. Among these, Acinetobacter baumannii, Acinetobacter nosocomialis, and Acinetobacter pittii are the most frequently isolated in hospitals around the world. Despite the growing incidence of multidrug-resistant Acinetobacter spp., little is known about the factors that contribute to pathogenesis. New strategies for treating and managing infections caused by multidrug-resistant Acinetobacter strains are urgently needed, and this requires a detailed understanding of the pathobiology of these organisms. In recent years, some virulence factors important for Acinetobacter colonization have started to emerge. In this review, we focus on several recently described virulence factors that act at the bacterial surface level, such as the capsule, O-linked protein glycosylation, and adhesins. Furthermore, we describe the current knowledge regarding the type II and type VI secretion systems present in these strains.

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OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections

Cited by 54 publications

References 31 publications

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

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