1887

Abstract

Infections caused by Gram-negative bacteria (GNB) are increasingly common and can result in significant mortality rates due to the development of sepsis. To examine the potential usage of a recombinant Ad5-BPI-Fcγ1 virus as a biological treatment against systemic infection by GNB, a construct containing the human bactericidal/permeability increasing protein (BPI) gene, encoding the functional N terminus (amino acid residues 1–199) of human BPI, and the Fcγ1 gene, encoding the Fc segment of human immunoglobulin G1, was inserted into an adenovirus serotype 5 (Ad5) chromosome to produce a recombinant Ad5-BPI-Fcγ1 virus. Human A549 cells in culture and BALB/c mice were infected with the recombinant Ad5-BPI-Fcγ1 virus and BPI-Fcγ1 expression was confirmed by Western blot analysis and ELISA. The concentrations of BPI-Fcγ1 protein were 5.59 µg ml and 21.37 ng ml and it was observed that these concentrations were sufficient to decrease endotoxin concentrations while enhancing bactericidal activity. In addition, mice treated with the recombinant Ad5-BPI-Fcγ1 virus had decreased levels of IL-1β and TNF-α and were protected from an O111 : B4 challenge. Our data support the concept that Ad5-mediated BPI-Fcγ1 gene delivery could be used as an ancillary biological treatment in the management of infection caused by GNB.

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2012-09-01
2019-10-21
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