Infecting mice with recombinant Ad5-BPI23-Fcγ1 virus protects against systemic Escherichia coli challenge
- 1 September 2012
- journal article
- Published by Microbiology Society in Journal of Medical Microbiology
- Vol. 61 (9), 1262-1269
- https://doi.org/10.1099/jmm.0.040907-0
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-BPI23-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-BPI23-Fcγ1 virus. Human A549 cells in culture and BALB/c mice were infected with the recombinant Ad5-BPI23-Fcγ1 virus and BPI23-Fcγ1 expression was confirmed by Western blot analysis and ELISA. The concentrations of BPI23-Fcγ1 protein were 5.59 µg ml−1 in vitro and 21.37 ng ml−1 in vivo 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-BPI23-Fcγ1 virus had decreased levels of IL-1β and TNF-α and were protected from an E. coli O111 : B4 challenge. Our data support the concept that Ad5-mediated BPI23-Fcγ1 gene delivery could be used as an ancillary biological treatment in the management of infection caused by GNB.Keywords
This publication has 21 references indexed in Scilit:
- Progress and prospects: immune responses to viral vectorsGene Therapy, 2009
- Protection of Mice from Lethal Escherichia coli Infection by ChimericHuman Bactericidal/Permeability-Increasing Protein and ImmunoglobulinG1 Fc Gene DeliveryAntimicrobial Agents and Chemotherapy, 2007
- Peptide Antimicrobial AgentsClinical Microbiology Reviews, 2006
- Prevalence of Neutralizing Antibodies to Adenoviral Serotypes 5 and 35 in the Adult Populations of The Gambia, South Africa, and the United StatesClinical and Vaccine Immunology, 2004
- Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing proteinBlood, 2004
- Lipopolysaccharide EndotoxinsAnnual Review of Biochemistry, 2002
- Expression of the K54 and O4 specific antigen has opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate ofEscherichia coliFEMS Microbiology Letters, 1998
- Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsisThe Lancet, 1997
- BIOCHEMISTRY OF ENDOTOXINSAnnual Review of Biochemistry, 1990
- NEW LIMULUS AMOEBOCYTE LYSATE TEST FOR ENDOTOXAEMIAThe Lancet, 1982