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遗传分析揭示了在比利时流行的人类轮状病毒与 Rotarix 和 RotaTeq 中轮状病毒之间 VP7 和 VP4 抗原表位的差异。

Genetic analyses reveal differences in the VP7 and VP4 antigenic epitopes between human rotaviruses circulating in Belgium and rotaviruses in Rotarix and RotaTeq.

机构信息

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.

出版信息

J Clin Microbiol. 2012 Mar;50(3):966-76. doi: 10.1128/JCM.05590-11. Epub 2011 Dec 21.

Abstract

Two live-attenuated rotavirus group A (RVA) vaccines, Rotarix (G1P[8]) and RotaTeq (G1-G4, P[8]), have been successfully introduced in many countries worldwide, including Belgium. The parental RVA strains used to generate the vaccines were isolated more than 20 years ago in France (G4 parental strain in RotaTeq) and the United States (all other parental strains). At present, little is known about the relationship between currently circulating human RVAs and the vaccine strains. In this study, we determined sequences for the VP7 and VP4 outer capsid proteins of representative G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] RVAs circulating in Belgium during 2007 to 2009. The analyses showed that multiple amino acid differences existed between the VP7 and VP4 antigenic epitopes of the vaccine viruses and the Belgian isolates, regardless of their G and P genotypes. However, the highest variability was observed among the circulating G1P[8] RVA strains and the G1 and P[8] components of both RVA vaccines. In particular, RVA strains of the P[8] lineage 4 (OP354-like) showed a significant number of amino acid differences with the P[8] VP4 of both vaccines. In addition, the circulating Belgian G3 RVA strains were found to possibly possess an extra N-linked glycosylation site compared to the G3 RVA vaccine strain of RotaTeq. These results indicate that the antigenic epitopes of RVA strains contained in the vaccines differ substantially from those of the currently circulating RVA strains in Belgium. Over time, these differences might result in selection for strains that escape the RVA neutralizing-antibody pressure induced by vaccines.

摘要

两种活减毒轮状病毒 A 型(RVA)疫苗,Rotarix(G1P[8])和 RotaTeq(G1-G4,P[8]),已在包括比利时在内的许多国家成功引进。用于生成疫苗的亲本 RVA 株系是 20 多年前在法国(RotaTeq 中的 G4 亲本株系)和美国(所有其他亲本株系)分离的。目前,人们对当前流行的人 RVA 与疫苗株之间的关系知之甚少。在这项研究中,我们确定了 2007 年至 2009 年期间在比利时流行的代表 G1P[8]、G2P[4]、G3P[8]、G4P[8]、G9P[8]和 G12P[8]RVA 的 VP7 和 VP4 外壳蛋白的序列。分析表明,无论其 G 和 P 基因型如何,疫苗病毒和比利时分离株的 VP7 和 VP4 抗原表位之间存在多个氨基酸差异。然而,在循环的 G1P[8]RVA 株系和两种 RVA 疫苗的 G1 和 P[8]成分之间观察到最高的变异性。特别是,P[8]谱系 4(OP354 样)的 RVA 株系与两种疫苗的 P[8]VP4 存在显著数量的氨基酸差异。此外,与 RotaTeq 中 G3 RVA 疫苗株相比,发现循环的比利时 G3 RVA 株系可能具有额外的 N-连接糖基化位点。这些结果表明,疫苗中包含的 RVA 株系的抗原表位与比利时目前流行的 RVA 株系有很大差异。随着时间的推移,这些差异可能导致逃避疫苗引起的 RVA 中和抗体压力的菌株选择。

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