Jpn. J. Infect. Dis., 64 (1), 40-49, 2011
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Original Article
Passive Immune-Prophylaxis against Influenza Virus Infection by the Expression of Neutralizing Anti-Hemagglutinin Monoclonal Antibodies from Plasmids
Tatsuya Yamazaki, Maria Nagashima, Daisuke Ninomiya, Yuka Arai, Yasutomo Teshima, Akira Fujimoto, Akira Ainai1, Hideki Hasegawa1, and Joe Chiba*
Department of Biological Science and Technology, Tokyo University of Science, Chiba 278-8510; and 1Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
(Received November 30, 2010. Accepted December 8, 2010)
*Corresponding author: Mailing address: Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. Tel & Fax: +81-4-7122-9695, E-mail: chibaj@rs.noda.tus.ac.jp
SUMMARY: 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.