PMID- 21178283
OWN - NLM
STAT- MEDLINE
DCOM- 20110328
LR  - 20101223
IS  - 1875-869X (Electronic)
IS  - 1093-2607 (Linking)
VI  - 19
IP  - 4
DP  - 2010
TI  - A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface 
      determinant B (IsdB) with functional activity in vitro and in vivo.
PG  - 113-28
LID - 10.3233/HAB-2010-0235 [doi]
AB  - A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated 
      surface determinant B (IsdB) of Staphylococcus aureus was isolated from the 
      Cambridge Antibody Technology (CAT) scFv antibody library. As compared to 
      previously described IsdB specific murine monoclonals, CS-D7 has a unique, 
      non-overlapping binding site on IsdB, and exhibits increased in vivo activity. 
      The antibody recognizes a conformational epitope spanning amino acids 50 to 285 
      and has a binding affinity of 340 (+/- 75) pM for IsdB. CS-D7 bound to a wide 
      variety of S. aureus strains, but not to an isdB deletion mutant. The antibody 
      mediated opsonophagocytic (OP) killing in vitro and mediated significant 
      protection in vivo. In a murine lethal sepsis model, the antibody conferred 
      protection from death when dosed prior to challenge, but not when dosed after 
      challenge. Importantly, in a central venous catheter (CVC) model in rats, the 
      antibody reduced bacteremia and prevented colonization of indwelling catheters. 
      Protection was observed when rats were dosed with CS-D7 prior to challenge as 
      well as post challenge. IsdB is currently being investigated for clinical 
      efficacy against S. aureus infection, and the activity of this human IsdB 
      specific antibody supplements the growing body of evidence to support targeting 
      this antigen for vaccine development.
FAU - Ebert, Tim
AU  - Ebert T
AD  - Merck Research Labs, Merck and Co. Inc., West Point, PA 19486, USA.
FAU - Smith, Sharon
AU  - Smith S
FAU - Pancari, Greg
AU  - Pancari G
FAU - Clark, Desmond
AU  - Clark D
FAU - Hampton, Richard
AU  - Hampton R
FAU - Secore, Susan
AU  - Secore S
FAU - Towne, Victoria
AU  - Towne V
FAU - Fan, Hongxia
AU  - Fan H
FAU - Wang, Xin-Min
AU  - Wang XM
FAU - Wu, Xiaoqing
AU  - Wu X
FAU - Ernst, Robin
AU  - Ernst R
FAU - Harvey, Barrett R
AU  - Harvey BR
FAU - Finnefrock, Adam C
AU  - Finnefrock AC
FAU - Wang, Fubao
AU  - Wang F
FAU - Tan, Charles
AU  - Tan C
FAU - Durr, Eberhard
AU  - Durr E
FAU - Cope, Leslie
AU  - Cope L
FAU - Anderson, Annaliesa
AU  - Anderson A
FAU - An, Zhiqiang
AU  - An Z
FAU - McNeely, Tessie
AU  - McNeely T
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Hum Antibodies
JT  - Human antibodies
JID - 9711270
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (IsdB protein, Staphylococcus aureus)
RN  - 0 (Opsonin Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Bacterial/immunology/metabolism
MH  - Antibodies, Monoclonal/*immunology/metabolism/*therapeutic use
MH  - Antibody Specificity
MH  - Bacteremia/immunology/microbiology/mortality/prevention & control
MH  - Catheterization, Central Venous/adverse effects
MH  - Cation Transport Proteins/genetics/*immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Opsonin Proteins/metabolism
MH  - Phagocytosis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sepsis/microbiology/mortality/prevention & control
MH  - Staphylococcal Infections/microbiology/*mortality/*prevention & control
MH  - Staphylococcus aureus/genetics/*immunology/pathogenicity
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2010/12/24 06:00
MHDA- 2011/03/29 06:00
CRDT- 2010/12/24 06:00
PHST- 2010/12/24 06:00 [entrez]
PHST- 2010/12/24 06:00 [pubmed]
PHST- 2011/03/29 06:00 [medline]
AID - X7G3821230461130 [pii]
AID - 10.3233/HAB-2010-0235 [doi]
PST - ppublish
SO  - Hum Antibodies. 2010;19(4):113-28. doi: 10.3233/HAB-2010-0235.