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首页> 外文期刊>Vaccine >Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU180
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Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU180

机译：六种单个VP4基因替代重配轮状病毒疫苗候选物的生成和表征：每个候选病毒携带一个编码P血清型1A [8]或1B [4]的人类轮状病毒VP4基因，以及恒河猴轮状病毒MMU180的其余10个基因

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摘要

The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype I A[8] or I B [4] specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.
机译：婴幼儿轮状病毒腹泻的全球疾病负担激发了人们对这些药物的生物学和临床特征的兴趣，从而导致人们大力开发疫苗。一种基于恒河猴轮状病毒（RRV）的四价疫苗（“ RotaShield”）已获许可并向约100万婴儿施用，被认为是高效的。但是，由于与肠套叠的关系而将其撤回。该疫苗是根据改良的“ Jennerian”方法开发的，其中两种主要外衣壳蛋白（VP7）之一与四种流行病学上重要的人类轮状病毒血清型之一具有中和特异性。其他外衣壳蛋白（VP4）仅源自RRV，与流行病学上重要的四种人类轮状病毒血清型的VP4不同。为了进一步提高现有基于VP7的RRV四价疫苗的免疫原性，我们制备了三种单VP4基因替代重配轮状病毒候选疫苗，每种疫苗都携带一个编码P血清型IA [8]或IB的人类轮状病毒VP4基因。 4]特异性，而其余10个基因均来自恒河猴轮状病毒。通过将其中一种或两种菌株掺入四价疫苗中，可以配制基于五价或六价RRV的疫苗，从而不仅为VP7血清型1、2、3和4提供抗原覆盖，而且为VP4血清型1A [8]提供抗原覆盖。 1B [4]，因此可能增强其免疫原性。同样，在10个牛（英国）轮状病毒基因的背景下，还产生了三个单一的VP4基因（P1A [8]或P1B [4]）替代重配子，以添加到基于第二代UK的四价疫苗中。

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