2018 年 21 巻 p. 7-11
Classical passive immunization has provided the benefit to prevent against infectious diseases for over century. Although lots of antibody-drugs have been developed for cancer and autoimmune disease, those against infectious disease are rarely available. Because it has complex reasons including the current availability of antimicrobial drugs, small markets, high costs, and microbial antigenic variation.
We firstly demonstrated long-prophylaxis against influenza virus (A/Puerto Rico/8/34, IAV) using plasmids encoding neutralizing IgG monoclonal antibodies. Antibody gene-based injection could induce stable and high expression level of the neutralizing antibodies, which was possible that single inoculation protected the mice against a lethal dose of IAV infection. We proposed that this method could dissolve problems of high cost to the purification, limited supply for pandemic, and the risk of using viral vectors.
We also succeeded to treatment against IAV infection using antibody gene-based injection by hydrodynamics (HD), which was involving rapid inoculation of a large volume of plasmid-DNA solution into mice via the tail vein. HD could rapidly induce the potent level of neutralizing antibodies in the serum within 24 hours. We demonstrated that a single HD completely protected the mice even after a lethal dose of IAV infection. Finally, we also generated other isotypes of antibody-gene to exchange from IgG to IgA, IgM, IgD, and IgE to retain the variable region. The neutralizing IgA was most effective at reducing upper respiratory tract IAV infection. Thus, our passive immunotherapy could provide a new prophylaxis/therapeutic strategy of targeting IAV infection.
