Target-Agnostic Identification of Functional Monoclonal Antibodies Against Klebsiella pneumoniae Multimeric MrkA Fimbrial Subunit.
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.
['Wang|Qun|Q|', 'Chang|Chew-Shun|CS|', 'Pennini|Meghan|M|', 'Pelletier|Mark|M|', 'Rajan|Saravanan|S|', 'Zha|Jingying|J|', 'Chen|Yan|Y|', 'Cvitkovic|Romana|R|', 'Sadowska|Agnieszka|A|', 'Heidbrink Thompson|Jenny|J|', 'Yu Lin|Hung|H|', 'Barnes|Arnita|A|', 'Rickert|Keith|K|', 'Wilson|Susan|S|', 'Stover|C Kendall|CK|', "Dall'Acqua|William F|WF|", 'Chowdhury|Partha S|PS|', 'Xiao|Xiaodong|X|']
D000818:Animals D000907:Antibodies, Bacterial D000911:Antibodies, Monoclonal D000918:Antibody Specificity D001428:Bacterial Vaccines D018441:Biofilms D003602:Cytotoxicity, Immunologic D036781:Fimbriae Proteins D006801:Humans D006825:Hybridomas D007710:Klebsiella Infections D007711:Klebsiella pneumoniae D051379:Mice D008810:Mice, Inbred C57BL D019151:Peptide Library D010587:Phagocytosis D020545:Respiratory Mucosa
monoclonal antibodies Klebsiella pneumoniae MrkA vaccine phage display hybridoma functional screening biofilm opsonophagocytic killing (OPK) organ burden