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呼吸道合胞病毒(RSV)G 蛋白疫苗与中央保守结构域突变诱导 CX3C-CX3CR1 阻断抗体。

Respiratory Syncytial Virus (RSV) G Protein Vaccines With Central Conserved Domain Mutations Induce CX3C-CX3CR1 Blocking Antibodies.

机构信息

Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA.

Department of Biomolecular Engineering, University of California-Santa Cruz, Santa Cruz, CA 95064, USA.

出版信息

Viruses. 2021 Feb 23;13(2):352. doi: 10.3390/v13020352.

Abstract

Respiratory syncytial virus (RSV) infection can cause bronchiolitis, pneumonia, morbidity, and some mortality, primarily in infants and the elderly, for which no vaccine is available. The RSV attachment (G) protein contains a central conserved domain (CCD) with a CX3C motif implicated in the induction of protective antibodies, thus vaccine candidates containing the G protein are of interest. This study determined if mutations in the G protein CCD would mediate immunogenicity while inducing G protein CX3C-CX3CR1 blocking antibodies. BALB/c mice were vaccinated with structurally-guided, rationally designed G proteins with CCD mutations. The results show that these G protein immunogens induce a substantial anti-G protein antibody response, and using serum IgG from the vaccinated mice, these antibodies are capable of blocking the RSV G protein CX3C-CX3CR1 binding while not interfering with CX3CL1, fractalkine.

摘要

呼吸道合胞病毒(RSV)感染可导致细支气管炎、肺炎、发病率和一定程度的死亡率,主要发生在婴儿和老年人中,目前尚无可用的疫苗。RSV 附着(G)蛋白包含一个中央保守结构域(CCD),其中含有一个 CX3C 基序,该基序与诱导保护性抗体有关,因此含有 G 蛋白的疫苗候选物引起了人们的兴趣。本研究确定 G 蛋白 CCD 中的突变是否会在诱导 G 蛋白 CX3C-CX3CR1 阻断抗体的同时介导免疫原性。用结构导向、合理设计的具有 CCD 突变的 G 蛋白对 BALB/c 小鼠进行了疫苗接种。结果表明,这些 G 蛋白免疫原能够诱导出大量的抗 G 蛋白抗体反应,并且使用接种小鼠的血清 IgG,这些抗体能够阻断 RSV G 蛋白 CX3C-CX3CR1 结合,而不干扰 CX3CL1、 fractalkine。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0616/7926521/62487bb97bc2/viruses-13-00352-g001.jpg

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