TY - JOUR
T1 - Anti-Ace monoclonal antibody reduces Enterococcus faecalis aortic valve infection in a rat infective endocarditis model
AU - Singh, Kavindra V.
AU - Pinkston, Kenneth L.
AU - Gao, Peng
AU - Harvey, Barrett R.
AU - Murray, Barbara E.
N1 - Funding Information:
∗Corresponding author: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 2.112, Houston, Texas 77030. Tel: +713-500-6758; Fax: +713-500-6745; E-mail: Kavindra.singh@uth.tmc.edu †Kavindra V. Singh and Kenneth L. Pinkston contributed equally to this work. ‡Current affiliation: Chief Operations Officer, IDA Therapeutics, LLC Houston, TX 77021. §Current affiliation: Chief Operations Officer, IDA Therapeutics, LLC Houston, TX 77021. K.V.S. has received grants from Paratek Pharmaceuticals and Merck. B.E.M. has received grants from Paratek Pharmaceuticals and Merck, and served on the advisory board for Cempra and Paratek. One sentence summary: Anti-Ace mAb70 prevents E. faecalis endocarditis in rats. Editor: Nicholas Carbonetti
Publisher Copyright:
© 2018 FEMS.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Ace (Adhesin to collagen from Enterococcus faecalis) is a cell-wall anchored protein that is expressed conditionally and is important for virulence in a rat infective endocarditis (IE) model. Previously, we showed that rats immunized with the collagen binding domain of Ace (domain A), or administered anti-Ace domain A polyclonal antibody, were less susceptible to E. faecalis endocarditis than sham-immunized controls. In this work, we demonstrated that a sub nanomolar monoclonal antibody (mAb), anti-Ace mAb 70, significantly diminished E. faecalis binding to ECM collagen IV in in vitro adherence assays and that, in the endocarditis model, anti-Ace mAb 70 pre-treatment significantly reduced E. faecalis infection of aortic valves. The effectiveness of anti-Ace mAb against IE in the rat model suggests it might serve as a beneficial agent for passive protection against E. faecalis infections.
AB - Ace (Adhesin to collagen from Enterococcus faecalis) is a cell-wall anchored protein that is expressed conditionally and is important for virulence in a rat infective endocarditis (IE) model. Previously, we showed that rats immunized with the collagen binding domain of Ace (domain A), or administered anti-Ace domain A polyclonal antibody, were less susceptible to E. faecalis endocarditis than sham-immunized controls. In this work, we demonstrated that a sub nanomolar monoclonal antibody (mAb), anti-Ace mAb 70, significantly diminished E. faecalis binding to ECM collagen IV in in vitro adherence assays and that, in the endocarditis model, anti-Ace mAb 70 pre-treatment significantly reduced E. faecalis infection of aortic valves. The effectiveness of anti-Ace mAb against IE in the rat model suggests it might serve as a beneficial agent for passive protection against E. faecalis infections.
KW - Enterococcus faecalis
KW - ace collagen adhesion
KW - immunoprophylaxis
KW - infective endocarditis
KW - pathogenesis
KW - protective vaccine
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U2 - 10.1093/femspd/fty084
DO - 10.1093/femspd/fty084
M3 - Article
C2 - 30445491
AN - SCOPUS:85061751099
VL - 76
JO - Pathogens and Disease
JF - Pathogens and Disease
SN - 2049-632X
IS - 8
M1 - fty084
ER -