Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 11, Pages 1800-1808Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw021
Keywords
Klebsiella pneumoniae; hybridoma; phage display; functional screening; monoclonal antibodies; MrkA; opsonophagocytic killing (OPK); biofilm; vaccine; organ burden
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Funding
- MedImmune
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The increasing incidence of Klebsiella pneumoniae infections refractory to treatment with current broad-spectrum antibiotic classes warrants the exploration of alternative approaches, such as antibody therapy and/or vaccines, for prevention and treatment. However, the lack of validated targets shared by spectrums of clinical strains poses a significant challenge. We adopted a target-agnostic approach to identify protective antibodies against K. pneumoniae. Several monoclonal antibodies were isolated from phage display and hybridoma platforms by functional screening for opsonophagocytic killing activity. We further identified their common target antigen to be MrkA, a major protein in the type III fimbriae complex, and showed that these serotype-independent anti-MrkA antibodies reduced biofilm formation in vitro and conferred protection in multiple murine pneumonia models. Importantly, mice immunized with purified MrkA proteins also showed reduced bacterial burden following K. pneumoniae challenge. Taken together, these results support MrkA as a promising target for K. pneumoniae antibody therapeutics and vaccines.
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