Article
作者: Sun, He-Ying ; Snider, Timothy A ; Anderson, Evan J ; Stobart, Christopher C ; Jadhao, Samadhan ; Anderson, Larry J ; Liang, Bo ; Koval, Michael ; Roe, Molly K ; Reed, Ryan C ; Lapp, Stacey A ; Rostad, Christina A ; Piantadosi, Anne ; Chen, Xuemin ; Young, Audrey R ; Taz, Azmain ; Moore, Martin L ; Hsiao, Hui-Mien ; Batista, Yara S ; Perez, Maria A
AbstractBackgroundRespiratory 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.MethodsTwo 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.ResultsBoth 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.ConclusionsRemoval of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity.