Protection of immuno-compromised mice from lethal infection of Klebsiella pneumonia by rAAV2-BPI23-Fcgamma1 gene transfer.
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.
Li
Jing
J
Department of Immunology, Capital Medical University, Beijing, China.
Kong
Qingli
Q
Lv
Zhe
Z
Guan
Yuanzhi
Y
Qiu
Yong
Y
Li
Chen
C
Sun
Mingjie
M
Liu
Zhenlong
Z
An
Yunqing
Y
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000627:therapeutic use*; D001798:Blood Proteins / Q000235:genetics / Q000627:therapeutic use*; D001835:Body Weight; D002452:Cell Count; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood; D000229:Dependovirus / Q000235:genetics*; D004731:Endotoxins / Q000097:blood; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000235:genetics* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000235:genetics / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D007710:Klebsiella Infections / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology / Q000382:microbiology; D015996:Survival Rate
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D016207:Cytokines; D004731:Endotoxins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018836:Inflammation Mediators; C021623:bactericidal permeability increasing protein