Adeno-Associated Virus Vector-Mediated Expression of Antirespiratory Syncytial Virus Antibody Prevents Infection in Mouse Airways.
Publication/Presentation Date
12-1-2021
Abstract
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.
Volume
32
Issue
23-24
First Page
1450
Last Page
1456
ISSN
1557-7422
Published In/Presented At
Tycko, J., Adam, V. S., Crosariol, M., Ohlstein, J., Sanmiguel, J., Tretiakova, A. P., Roy, S., Worgall, S., Wilson, J. M., & Limberis, M. P. (2021). Adeno-Associated Virus Vector-Mediated Expression of Antirespiratory Syncytial Virus Antibody Prevents Infection in Mouse Airways. Human gene therapy, 32(23-24), 1450–1456. https://doi.org/10.1089/hum.2021.079
Disciplines
Medicine and Health Sciences
PubMedID
34415793
Department(s)
Department of Surgery
Document Type
Article