Abstract
Objective Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections.MethodsMice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay.ResultsIntramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates.ConclusionsUtilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections.
Highlights
Acinetobacter baumannii is a non-fermenting, Gram-negative, aerobic coccobacillus that is currently a major cause of nosocomial infections worldwide
Immunization with outer membrane vesicles (OMVs) produces a high level of persistent IgG responses to A. baumannii
Each mouse was immunized intramuscularly three times on days 0, 15, and 36 with OMVs prepared from strain Ab1, and the challenge with the homologue strain A. baumannii occurred 11 days after the last immunization
Summary
Acinetobacter baumannii is a non-fermenting, Gram-negative, aerobic coccobacillus that is currently a major cause of nosocomial infections worldwide. Epidemics caused by multidrug-resistant strains of A. baumannii have been widely investigated and reported [1,2]. Immunological strategies, which may function through approaches that differ from that of antibiotics and hopefully circumvent complex multidrug-resistant mechanisms, are emerging as a viable option. Several studies have shown that various vaccine candidates have an effect on controlling A. baumannii infections [7,8,9,10,11,12,13]. Single outer membrane proteins, OmpA [12,14], Bap [15], and Ata [11], have been identified as effective candidate vaccines that immunologically intervene in A. baumannii infection
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