Protection of immuno-compromised mice from lethal infection of Klebsiella pneumonia by rAAV2-BPI23-Fcgamma1 gene transfer.

Abstract:

:In previous research, chimerical BPI23-Fcgamma1 gene which consisted of human bactericidal/permeability increasing protein (BPI) gene of encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and Fcgamma1 gene of encoding the Fc segment of human immunoglobulin G1 was successfully reconstructed within a recombinant adeno-associated virus serotype 2 (rAAV2) vector as rAAV2-BPI23-Fcgamma1. Here, to evaluate the potentiality of applying gene therapy to gram negative bacterial (GNB) infection in high-risk patients, we investigated protection of immuno-compromised mice and immunocompetent mice from challenge with minimal lethal dose (MLD) Klebsiella pneumonia infection after rAAV2-BPI23-Fcgamma1 gene transferred. The results showed that the survival rate of rAAV2-BPI23-Fcgamma1 transferred immunocompetent mice as well as immuno-compromised mice (40.0% and 44.4%, respectively) were significantly higher than that of corresponding control mice (6.7% and 4.4%, respectively); the bacteria counting, level of endotoxin and proinflammatory cytokines in the rAAV2-BPI23-Fcgamma1 transferred immuno-compromised mice were markedly lower than that of rAAV2-EGFP and rAAV2-Null transferred immuno-compromised mice. Our data suggest that rAAV2-BPI23-Fcgamma1 gene transferring offered immuno-compromised mice with resistance against GNB infection, so it is quite potential in preventing GNB infection of clinical high-risk patients.

journal_name

Cell Mol Immunol

authors

Li J,Kong Q,Lv Z,Guan Y,Qiu Y,Li C,Sun M,Liu Z,An Y

doi

10.1038/cmi.2008.55

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

439-45

issue

6

eissn

1672-7681

issn

2042-0226

journal_volume

5

pub_type

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