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

Respiratory Syncytial Virus (RSV) G Protein Vaccines With Central Conserved Domain Mutations Induce CX3C-CX3CR1 Blocking Antibodies.
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DOI:
10.3390/v13020352
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发表时间:
2021-02-23
期刊:
Viruses
影响因子:
--
通讯作者:
Tripp RA
Tripp RA
中科院分区:
其他
文献类型:
--
作者:
Bergeron HC;Murray J;Nuñez Castrejon AM;DuBois RM;Tripp RA

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呼吸道合胞病毒(RSV)感染可引起毛细支气管炎、肺炎、发病率和一些死亡率,主要发生在没有疫苗的婴儿和老年人中。RSV附着蛋白(G)含有一个中心保守结构域(CCD),其CX3C基序与保护性抗体的诱导有关,因此含有G蛋白的候选疫苗是人们感兴趣的。本研究确定G蛋白CCD突变是否介导免疫原性,同时诱导G蛋白CX3C-CX3CR1阻断抗体。用结构引导、合理设计的具有CCD突变的G蛋白接种BALB/c小鼠。结果表明,这些G蛋白免疫原诱导了大量的抗G蛋白抗体反应,并且利用接种小鼠的血清IgG,这些抗体能够阻断RSV G蛋白CX3C-CX3CR1的结合,而不干扰CX3CL1, fractalkine。
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.
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