Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii

Abstract

A. baumannii infections are becoming more and more serious health issues with rapid emerging of multidrug and extremely drug resistant strains, and therefore, there is an urgent need for the development of nonantibiotic-based intervention strategies. This study aimed at identifying whether an outer membrane protein with molecular weight of about 22 kDa (Omp22) holds the potentials to be an efficient vaccine candidate and combat A. baumannii infection. Omp22 which has a molecule length of 217 amino acids kept more than 95% conservation in totally 851 reported A. baumannii strains. Recombinant Omp22 efficiently elicited high titers of specific IgG in mice. Both active and passive immunizations of Omp22 increased the survival rates of mice, suppressed the bacterial burdens in the organs and peripheral blood, and reduced the levels of serum inflammatory cytokines and chemokines. Opsonophagocytosis assays showed in vitro that Omp22 antiserum had highly efficient bactericidal activities on clonally distinct clinical A. baumannii isolates, which were partly complements-dependent and opsonophagocytic killing effects. Additionally, administration with as high as 500 μg of Omp22 didn’t cause obvious pathological changes in mice. In conclusion, Omp22 is a novel conserved and probably safe antigen for developing effective vaccines or antisera to control A. baumannii infections.

The Capsular Polysaccharide of Acinetobacter baumannii Is an Obstacle for Therapeutic Passive Immunization Strategies

“…baumannii has emerged as perhaps the most troubling pathogen globally due to the increasing prevalence of XDR strains and the paucity of antimicrobials active against A. baumannii in the drug development pipeline (25,26). Passive immunizations with polyclonal antisera targeting OMPs of A. baumannii, such as OmpA, Omp22, and OMP complexes, have shown protection against clinical isolates in mouse sepsis models (9,11,12). These promising animal study results suggested a new therapeutic modality for the treatment of A. baumannii infections.…”

“…Recently, active immunization with outer membrane protein A (OmpA) and passive immunization with polyclonal anti-OmpA sera have shown promising protection against multidrug-resistant (MDR) and XDR A. baumannii clinical isolates in a mouse bacteremia model (9,10). Further, passive immunization with polyclonal antisera that target other OMPs, such as Omp22 and outer membrane complexes, also conferred protection against MDR A. baumannii in a mouse sepsis model (11,12). However, treatment with polyclonal antisera has inevitable drawbacks, including "serum sickness" or immune complex hypersensitivity that can occur in 10 to 50% of patients, lot-to-lot variation in efficacy, low content of specific antibodies, and potential hazards in the transmission of infectious diseases (13)(14)(15)(16).…”

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

“…In this study, the non-pathogenic E. coli DH5 α strain was employed to prepare engineered OMVs displaying a previously identified immunogenic outer membrane protein of A. baumannii, Omp2224, which served as a representative antigen. Utilizing the intrinsic immunological and structural features of OMVs, we sought to investigate whether the engineered OMVs can present a functional heterologous protein, induce high titers of specific antibodies, and provide significant immune protection against lethal challenge with A. baumannii in a murine sepsis model, and thus to demonstrate the potential of using E. coli OMVs as a feasible antigen delivery platform.…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

“…Omp22 is more than 95% conserved within 851 reported A. baumannii strains [171]. In contrast, there is no homology with human proteins.…”

“…This unique and conserved sequence makes Omp22 an ideal vaccine candidate. Immunization of mice with recombinant Omp22 induced clear protection from MDR A. baumannii infections, showing a potential vaccine candidate [171].…”