一种缺乏 G 蛋白黏液结构域的 RSV 活疫苗候选物具有减毒、免疫原性，并能有效预防 BALB/c 小鼠 RSV。
An RSV Live-Attenuated Vaccine Candidate Lacking G Protein Mucin Domains Is Attenuated, Immunogenic, and Effective in Preventing RSV in BALB/c Mice.
机构信息
Department of Biological Sciences, Butler University, Indianapolis, Indiana, USA.
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
出版信息
J Infect Dis. 2022 Dec 28;227(1):50-60. doi: 10.1093/infdis/jiac382.
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.
背景
呼吸道合胞病毒（RSV）是婴儿中主要的病毒性呼吸道病原体。本研究的目的是通过去除 G 蛋白黏液结构域来产生 RSV 减毒活疫苗（LAV）候选物，从而在保留免疫原性的同时减弱病毒复制，通过暴露表面表位来实现减毒。
方法
通过删除 G 蛋白黏液结构域（A2-line19F-G155）或删除 G 蛋白黏液和跨膜结构域（A2-line19F-G155S），从重组 RSV A2-line19F 中生成了两种 LAV 候选物。通过荧光焦点单位（FFU）测定和实时聚合酶链反应（RT-PCR）在 BALB/c 小鼠肺部测定疫苗减毒作用。通过在第 28 天和第 59 天进行初次/加强免疫后测量小鼠血清结合和中和抗体来确定免疫原性。通过在攻毒后第 4 天测量 RSV 肺部病毒载量来确定功效。
结果
两种 LAV 均不能通过 FFU 测定在小鼠肺部检测到，与 A2-line19F 相比，在第 28 天和第 59 天诱导的中和抗体滴度相似。在 RSV 攻毒后，通过 FFU 测定，接种疫苗的小鼠肺部未检测到 RSV，通过 RT-PCR 检测，A2-line19F-G155 组和 A2-line19F-G155S 组肺部 RSV RNA 分别降低 560 倍和 604 倍，与未接种疫苗的 RSV 攻毒小鼠相比，肺部 RSV RNA 显著降低。
结论
去除 G 蛋白黏液结构域产生了 RSV LAV 候选物，这些候选物具有高度减毒作用，同时保留了免疫原性。
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