Passive immune-prophylaxis against influenza virus infection by the expression of neutralizing anti-hemagglutinin monoclonal antibodies from plasmids.
The genetic delivery of therapeutic monoclonal antibodies (mAbs) by in vivo production may offer a new solution to the current problems in the mAb therapy for microbial diseases. Herein, plasmids encoding the neutralizing mAb against hemagglutinin (HA) of A/PR/8/34 influenza virus (IFV) were electro-transferred into mouse muscle and the relationship between serum recombinant anti-HA mAb (rHA mAb) levels and the prophylactic efficacy against lethal IFV infection were analyzed. Pretreatment of the muscle with hyaluronidase before electroporation and gene transfer into 3 muscles resulted in a marked enhancement of the mAb expression. After single gene transfer, peak serum concentrations were reached around 20 days after the gene transfer following sustained expression of >10 µg/ml of rHA mAbs. This level of rHA mAb expression was sufficient to protect all mice against a lethal IFV infection. Furthermore, a significant rHA mAb expression level sufficient to protect the host against lethal IFV infection was maintained for at least 130 days. Passive immune-prophylaxis with gene transfer using the plasmid encoding neutralizing mAbs may therefore provide effective protection against viral infections, including IFV.
Department of Biological Science and Technology, Tokyo University of Science, Chiba 278-8510, Japan.
Tatsuya
T
Yamazaki
Maria
M
Nagashima
Daisuke
D
Ninomiya
Yuka
Y
Arai
Yasutomo
Y
Teshima
Akira
A
Fujimoto
Akira
A
Ainai
Hideki
H
Hasegawa
Joe
J
Chiba
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018890:Chemoprevention; D018274:Electroporation; D018014:Gene Transfer Techniques; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010957:Plasmids / Q000235:genetics*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines