The K1 capsular polysaccharide from Acinetobacter baumannii Is a potential therapeutic target via passive immunization

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DOIResolve DOI: http://doi.org/10.1128/IAI.01184-12
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TypeArticle
Journal titleInfection and Immunity
ISSN0019-9567
Volume81
Issue3
Pages915922; # of pages: 8
Subjectepitope; K1 capsular polysaccharide; monoclonal antibody; polysaccharide; unclassified drug; Acinetobacter baumannii; animal experiment; animal model; article; bacterial capsule; bacterial clearance; bacterial growth; bacterial strain; bacterial survival; bactericidal activity; carbohydrate analysis; controlled study; immunogenicity; male; mass spectrometry; molecular mimicry; mouse; neutrophil; nonhuman; nuclear magnetic resonance; opsonization; passive immunization; priority journal; rat; seroprevalence; serotype; soft tissue infection; Acinetobacter baumannii; Acinetobacter Infections; Animals; Antibodies, Monoclonal; Bacterial Capsules; Bacterial Vaccines; Epitopes; Flow Cytometry; Gene Expression Regulation, Bacterial; Immunization, Passive; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Rats; Rats, Long-Evans
AbstractThe emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials. © 2013, American Society for Microbiology.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269590
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Record identifier2736793c-658d-4053-acfa-cbe77b1f59a9
Record created2013-12-13
Record modified2016-05-09
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