Neutralizing Anti-Hemagglutinin Monoclonal Antibodies Induced by Gene-Based Transfer Have Prophylactic and Therapeutic Effects on Influenza Virus Infection
| Autor: | Tatsuya Yamazaki, Sachiko Akashi-Takamura, Joe Chiba |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
passive immune-therapy medicine.drug_class viruses Genetic enhancement Immunology lcsh:Medicine passive immune-prophylaxis plasmid vector Hemagglutinin (influenza) Review Monoclonal antibody Virus 03 medical and health sciences Plasmid hydrodynamic injection Drug Discovery medicine Pharmacology (medical) hemagglutinin Pharmacology biology adeno-associated virus (AAV) vector lcsh:R Vaccine efficacy gene therapy Virology 030104 developmental biology Infectious Diseases Immunization antibody-gene biology.protein antibody drug electro-transfer Antibody |
| Zdroj: | Vaccines Vaccines, Vol 6, Iss 3, p 35 (2018) |
| ISSN: | 2076-393X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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