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Vaccines 2018, 6(3), 35; https://doi.org/10.3390/vaccines6030035

Neutralizing Anti-Hemagglutinin Monoclonal Antibodies Induced by Gene-Based Transfer Have Prophylactic and Therapeutic Effects on Influenza Virus Infection

1
Department of Microbiology and Immunology, Aichi Medical University, School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, Tokyo 480-1195, Japan
2
Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585, Japan
*
Author to whom correspondence should be addressed.
Received: 11 June 2018 / Revised: 23 June 2018 / Accepted: 25 June 2018 / Published: 26 June 2018
(This article belongs to the Special Issue The Role of Hemagglutinin in Influenza Viruses Infection)
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Abstract

Hemagglutinin (HA) of influenza virus is a major target for vaccines. HA initiates the internalization of the virus into the host cell by binding to host sialic acid receptors; therefore, inhibition of HA can significantly prevent influenza virus infection. However, the high diversity of HA permits the influenza virus to escape from host immunity. Moreover, the vaccine efficacy is poor in some high-risk populations (e.g., elderly or immunocompromised patients). Passive immunization with anti-HA monoclonal antibodies (mAbs) is an attractive therapy; however, this method has high production costs and requires repeated inoculations. To address these issues, several methods for long-term expression of mAb against influenza virus have been developed. Here, we provide an overview of methods using plasmid and viral adeno-associated virus (AAV) vectors that have been modified for higher expression of neutralizing antibodies in the host. We also examine two methods of injection, electro-transfer and hydrodynamic injection. Our results show that antibody gene transfer is effective against influenza virus infection even in immunocompromised mice, and antibody expression was detected in the serum and upper respiratory tract. We also demonstrate this method to be effective following influenza virus infection. Finally, we discuss the perspective of passive immunization with antibody gene transfer for future clinical trials. View Full-Text
Keywords: hemagglutinin; antibody drug; passive immune-prophylaxis; passive immune-therapy; antibody-gene; gene therapy; plasmid vector; adeno-associated virus (AAV) vector; electro-transfer; hydrodynamic injection hemagglutinin; antibody drug; passive immune-prophylaxis; passive immune-therapy; antibody-gene; gene therapy; plasmid vector; adeno-associated virus (AAV) vector; electro-transfer; hydrodynamic injection
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yamazaki, T.; Chiba, J.; Akashi-Takamura, S. Neutralizing Anti-Hemagglutinin Monoclonal Antibodies Induced by Gene-Based Transfer Have Prophylactic and Therapeutic Effects on Influenza Virus Infection. Vaccines 2018, 6, 35.

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