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

摘要

In previous research, chimerical BPI23-Fcγ1 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 Fcγ1 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-Fcγ1. 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-Fcγ1 gene transferred. The results showed that the survival rate of rAAV2-BPI23-Fcγ1 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- Fcγ1 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-Fcγ1 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.