抗体遺伝子を用いたウイルス感染症制御への挑戦

抄録

 The genetic delivery of therapeutic monoclonal antibodies (mAbs) by in vivo production would be a new candidate for controlling virus infection, because it can overcome problems of high cost and limited supply in conventional protein-based antibody. We firstly performed electroporation using the plasmid encoding neutralizing IgG mAbs against hemagglutinin (HA) of A/PR/8/34 influenza virus (IAV) (EP). We succeeded to induce high level of neutralizing antibodies (approx.10 µg/ml) in mouse serum with a single dose for at least 70 days, and obtaining long-prophylactic effect against a lethal dose of IAV infection for 130 days. We next established a new method of passive immunotherapy after IAV infection. We performed hydrodynamic injection, which involve rapid injection of a large volume of plasmid-DNA solution into mice via the tail vein, using the neutralizing mAbs-expressing plasmids (HD). HD could more rapidly induce the mAbs in the serum than in EP. We also showed that a single HD could significantly protect the mice at least 2 days after the lethal dose of IAV infection.

 Radioprotective 105 (RP105) is an orphan TLR family member. The agonistic anti-RP105 mAb can provide the potent proliferation of B cells and adjuvant effect, inducing higher levels of antigen-specific antibodies compared to alum. We also generated genetic constructs of recombinant anti-RP105 mAb. By vaccination with the plasmids encoding anti-RP105 mAb and HA into mice, we obtained significantly HA-specific antibodies and observed protective effects against the lethal infection. Antibody gene transfer could thus provide a new therapeutic strategy targeting virus infection.