使用四价恒河猴轮状病毒（RRV）和人-RRV重配疫苗，采用詹纳式及改良詹纳式方法预防轮状病毒腹泻。
Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine.
作者信息
Kapikian A Z, Hoshino Y, Chanock R M, Perez-Schael I
机构信息
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
出版信息
Arch Virol Suppl. 1996;12:163-75. doi: 10.1007/978-3-7091-6553-9_18.
Rotaviruses are the single most important cause of severe diarrhea of infants and young children world-wide. Deaths from rotavirus diarrhea occur infrequently in developed countries; however, in developing countries, rotaviruses are estimated to cause over 870000 deaths in the under five-year age group. There is, therefore, a vital need for a vaccine to prevent severe rotavirus diarrhea in infants and young children. The most extensively evaluated strategy for rotavirus vaccination has been the "Jennerian" approach in which an antigenically related rotavirus strain from an animal host (bovine or simian [rhesus monkey]) is used as the immunogen to induce protection against the four epidemiologically important group A human rotavirus serotypes. These orally administered vaccines were safe and immunogenic but had only limited success because serotype-specific immunity was not induced consistently in the under six-month age group. Therefore, a modified "Jennerian" approach was adopted with the goal of attaining broader antigenic coverage. In this approach four serotypes are combined to form a quadrivalent vaccine comprised of (i) rhesus rotavirus (RRV) which provides coverage for VP7 serotype 3, and (ii) three human-RRV reassortants each with ten RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. This modified "Jennerian" approach appears to be quite promising in preventing severe diarrhea in field trials. However, if this approach fails to yield an optimal level of protection consistently, additional modified "Jennerian" strategic, are under development that consider not only human rotavirus VP7 but also human rotavirus VP4, the other outer capsid protein. In addition, a non-"Jennerian" approach includes the development of cold-adapted human rotavirus strains or cold-adapted human rotavirus reassortants as vaccine candidates.
轮状病毒是全球婴幼儿严重腹泻的首要病因。在发达国家，轮状病毒腹泻导致的死亡并不常见；然而，在发展中国家，据估计轮状病毒在五岁以下年龄组中导致超过870000人死亡。因此，迫切需要一种疫苗来预防婴幼儿严重的轮状病毒腹泻。针对轮状病毒疫苗评估最广泛的策略是“詹纳式”方法，即使用来自动物宿主（牛或猿猴[恒河猴]）的抗原相关轮状病毒株作为免疫原，以诱导针对四种具有重要流行病学意义的A组人类轮状病毒血清型的保护作用。这些口服疫苗安全且具有免疫原性，但仅取得了有限的成功，因为在六个月以下年龄组中不能始终诱导出血清型特异性免疫。因此，为了实现更广泛的抗原覆盖范围，采用了改良的“詹纳式”方法。在这种方法中，四种血清型组合形成一种四价疫苗，该疫苗由（i）恒河猴轮状病毒（RRV）组成，它可覆盖VP7血清型3，以及（ii）三种人-RRV重配病毒，每种重配病毒都有十个RRV基因和一个编码VP7血清型1、2或4特异性的单个人类轮状病毒基因。这种改良的“詹纳式”方法在现场试验中预防严重腹泻方面似乎很有前景。然而，如果这种方法不能始终产生最佳保护水平，正在开发其他改良的“詹纳式”策略，这些策略不仅考虑人类轮状病毒VP7，还考虑人类轮状病毒VP4（另一种外衣壳蛋白）。此外，一种非“詹纳式”方法包括开发冷适应的人类轮状病毒株或冷适应的人类轮状病毒重配病毒作为候选疫苗。
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