Adeno-Associated Virus Vector-Mediated Expression of Antirespiratory Syncytial Virus Antibody Prevents Infection in Mouse Airways
| Autor: | Jason Ohlstein, Julio Sanmiguel, Marco Crosariol, Anna Tretiakova, Stefan Worgall, Maria P. Limberis, Virginie S. Adam, Josh Tycko, Soumitra Roy, James M. Wilson |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Palivizumab
Serotype viruses Respiratory Syncytial Virus Infections medicine.disease_cause Antiviral Agents Virus Mice Motavizumab Genetics medicine Animals Vector (molecular biology) Lung Molecular Biology Adeno-associated virus Mice Inbred BALB C biology business.industry Dependovirus Virology biology.protein Molecular Medicine Antibody business Viral load medicine.drug |
| Zdroj: | Human Gene Therapy. 32:1450-1456 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.2021.079 |
| Popis: | Infants and older adults are especially vulnerable to infection by respiratory syncytial virus (RSV), which can cause significant illness and irreparable damage to the lower respiratory tract and for which an effective vaccine is not readily available. Palivizumab, a recombinant monoclonal antibody (mAb), is an approved therapeutic for RSV infection for use in high-risk infants only. Due to several logistical issues, including cost of goods and scale-up limitations, palivizumab is not approved for other populations that are vulnerable to severe RSV infections, such as older adults. In this study, we demonstrate that intranasal delivery of adeno-associated virus serotype 9 (AAV9) vector expressing palivizumab or motavizumab, a second-generation version of palivizumab, significantly reduced the viral load in the lungs of the BALB/c mouse model of RSV infection. Notably, we demonstrate that AAV9 vector-mediated prophylaxis against RSV was effective despite the presence of serum-circulating neutralizing AAV9 antibodies. These findings substantiate the feasibility of repeatedly administering AAV9 vector to the airway for seasonal prophylaxis against RSV, thereby expanding the application of vectored delivery of mAbs as an effective prophylaxis strategy against various airborne viruses. |
| Databáze: | OpenAIRE |
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