Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella Pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

Long‐term anti‐endotoxin/E. coli efficacy in mice transfected with AAV2/1‐muBPI25‐muFcγ1

“…We have also observed similar protective effects of AAV-hBPI 23 -Fc in an immune-compromised mouse model challenged with MLD of E coli (17). These observations suggest that the application of AAV2-hBPI 23 -Fc might also have a protective effect in immune-compromised patients against GNB infection (17).…”

“…In addition, the mice transfected with AAV-hBPI 23 -Fc show increased resistance to minimal lethal dose (MLD) of endotoxin and increased survival rate (15,16). We have also observed similar protective effects of AAV-hBPI 23 -Fc in an immune-compromised mouse model challenged with MLD of E coli (17). These observations suggest that the application of AAV2-hBPI 23 -Fc might also have a protective effect in immune-compromised patients against GNB infection (17).…”

Fusion of the Fc part of human IgG1 to CD14 enhances its binding to Gram-negative bacteria and mediates phagocytosis by Fc receptors of neutrophils

“…We anticipated a similar effect in the case of CD14 so we created a CD14/Fc fusion protein -and a CD14/His protein as control -to evaluate their binding properties to whole microbes. We hoped that a CD14/Fc dimer has not only a higher affinity to whole bacteria but also an opsonizing effect via the Fc part as it has been described for similar fusion proteins [18,19,[21][22][23]28,29]. The presence of the Fc part may confer additional effector functions like complement activation or binding to FcRs on phagocytes [27].…”

“…Warren and his co-workers conjugated chemically the LPS-binding domain of CAP18 -a cationic antibacterial protein -and whole human IgG [18,21,28]. An and his co-workers coupled bactericidal permeability increasing protein (BPI) to the Fc part of human IgG on DNA level and expressed the construct both in vitro and in vivo [19,22,23]. In a recent report, Falk and co-workers created an LPS-Trap-Fc fusion protein, that consisted of the extracellular domain of TLR4 and MD2 fused to Fc portion of human IgG [29].…”

“…The advantage of coupling proteins to the Fc part of human IgG1 is their prolonged in vivo half-life time, decrease in renal toxicity and possible opsonizing properties which may lead to activation of the complement system and Fc receptors [20,21]. The use of cationic proteins as a part of such an antimicrobial fusion molecule seems to be very effective [18,19,[21][22][23].…”