Passive Immune-Prophylaxis against Influenza Virus Infection by the Expression of Neutralizing Anti-Hemagglutinin Monoclonal Antibodies from Plasmids

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  • Yamazaki Tatsuya
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Nagashima Maria
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Ninomiya Daisuke
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Arai Yuka
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Teshima Yasutomo
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Fujimoto Akira
    Department of Biological Science and Technology, Tokyo University of Science, Japan
  • Ainai Akira
    Influenza Virus Research Center, National Institute of Infectious Diseases, Japan
  • Hasegawa Hideki
    Influenza Virus Research Center, National Institute of Infectious Diseases, Japan
  • Chiba Joe
    Department of Biological Science and Technology, Tokyo University of Science, Japan

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<p>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.<tt> </tt></p>

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