PMID- 29416543 OWN - NLM STAT- MEDLINE DCOM- 20190214 LR - 20190215 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Neutralizing Antibodies Induced by Gene-Based Hydrodynamic Injection Have a Therapeutic Effect in Lethal Influenza Infection. PG - 47 LID - 10.3389/fimmu.2018.00047 [doi] LID - 47 AB - The influenza virus causes annual epidemics and occasional pandemics and is thus a major public health problem. Development of vaccines and antiviral drugs is essential for controlling influenza virus infection. We previously demonstrated the use of vectored immune-prophylaxis against influenza virus infection. We generated a plasmid encoding neutralizing IgG monoclonal antibodies (mAbs) against A/PR/8/34 influenza virus (IAV) hemagglutinin (HA). We then performed electroporation of the plasmid encoding neutralizing mAbs (EP) in mice muscles and succeeded in inducing the expression of neutralizing antibodies in mouse serum. This therapy has a prophylactic effect against lethal IAV infection in mice. In this study, we established a new method of passive immunotherapy after IAV infection. We performed hydrodynamic injection of the plasmid encoding neutralizing mAbs (HD) involving rapid injection of a large volume of plasmid-DNA solution into mice via the tail vein. HD could induce neutralizing antibodies in the serum and in several mucosal tissues more rapidly than in EP. We also showed that a single HD completely protected the mice even after infection with a lethal dose of IAV. We also established other isotypes of anti-HA antibody (IgA, IgM, IgD, and IgE) and showed that like anti-HA IgG, anti-HA IgA was also effective at combating upper respiratory tract IAV infection. Passive immunotherapy with HD could thus provide a new therapeutic strategy targeting influenza virus infection. FAU - Yamazaki, Tatsuya AU - Yamazaki T AD - Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Japan. AD - Department of Biological Science and Technology, Tokyo University of Science, Katsushika, Japan. FAU - Nagashima, Maria AU - Nagashima M AD - Department of Biological Science and Technology, Tokyo University of Science, Katsushika, Japan. FAU - Ninomiya, Daisuke AU - Ninomiya D AD - Department of Biological Science and Technology, Tokyo University of Science, Katsushika, Japan. FAU - Ainai, Akira AU - Ainai A AD - Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Japan. FAU - Fujimoto, Akira AU - Fujimoto A AD - Department of Biological Science and Technology, Tokyo University of Science, Katsushika, Japan. FAU - Ichimonji, Isao AU - Ichimonji I AD - Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Japan. FAU - Takagi, Hidekazu AU - Takagi H AD - Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Japan. FAU - Morita, Naoko AU - Morita N AD - Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Japan. FAU - Murotani, Kenta AU - Murotani K AD - Division of Biostatistics, Clinical Research Center, School of Medicine, Aichi Medical University, Nagakute, Japan. FAU - Hasegawa, Hideki AU - Hasegawa H AD - Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Japan. FAU - Chiba, Joe AU - Chiba J AD - Department of Biological Science and Technology, Tokyo University of Science, Katsushika, Japan. FAU - Akashi-Takamura, Sachiko AU - Akashi-Takamura S AD - Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180124 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Hemagglutinin Glycoproteins, Influenza Virus) RN - 0 (Influenza Vaccines) SB - IM MH - Animals MH - Antibodies, Neutralizing/genetics/*immunology MH - Antibodies, Viral/genetics/*immunology MH - Electroporation MH - Female MH - Hemagglutinin Glycoproteins, Influenza Virus/*immunology MH - Hydrodynamics MH - Immunization, Passive MH - Influenza Vaccines/*administration & dosage MH - Injections MH - Mice, Inbred BALB C MH - Orthomyxoviridae Infections/*therapy MH - Plasmids MH - Respiratory Mucosa/immunology/virology PMC - PMC5787536 OTO - NOTNLM OT - gene therapy OT - hemagglutinin OT - hydrodynamics procedure OT - influenza OT - neutralizing antibody OT - passive immunotherapy EDAT- 2018/02/09 06:00 MHDA- 2018/02/09 06:01 PMCR- 2018/01/01 CRDT- 2018/02/09 06:00 PHST- 2017/06/29 00:00 [received] PHST- 2018/01/08 00:00 [accepted] PHST- 2018/02/09 06:00 [entrez] PHST- 2018/02/09 06:00 [pubmed] PHST- 2018/02/09 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.00047 [doi] PST - epublish SO - Front Immunol. 2018 Jan 24;9:47. doi: 10.3389/fimmu.2018.00047. eCollection 2018.