| Autor: |
Molly K Roe, Maria A Perez, Hui-Mien Hsiao, Stacey A Lapp, He-Ying Sun, Samadhan Jadhao, Audrey R Young, Yara S Batista, Ryan C Reed, Azmain Taz, Anne Piantadosi, Xuemin Chen, Bo Liang, Michael Koval, Timothy A Snider, Martin L Moore, Evan J Anderson, Larry J Anderson, Christopher C Stobart, Christina A Rostad |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
The Journal of infectious diseases. 227(1) |
| ISSN: |
1537-6613 |
| Popis: |
Background Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes. Methods Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S). Vaccine attenuation was measured in BALB/c mouse lungs by fluorescent focus unit (FFU) assays and real-time polymerase chain reaction (RT-PCR). Immunogenicity was determined by measuring serum binding and neutralizing antibodies in mice following prime/boost on days 28 and 59. Efficacy was determined by measuring RSV lung viral loads on day 4 postchallenge. Results Both LAVs were undetectable in mouse lungs by FFU assay and elicited similar neutralizing antibody titers compared to A2-line19F on days 28 and 59. Following RSV challenge, vaccinated mice showed no detectable RSV in the lungs by FFU assay and a significant reduction in RSV RNA in the lungs by RT-PCR of 560-fold for A2-line19F-G155 and 604-fold for A2-line19F-G155S compared to RSV-challenged, unvaccinated mice. Conclusions Removal of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
