Pediatric Clinic, Department of Medicine and Surgery, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy.
Università degli Studi di Milano, Milan, Italy.
Front Immunol. 2020 Jul 7;11:1383. doi: 10.3389/fimmu.2020.01383. eCollection 2020.
Soon after its identification, norovirus (NoV) has been indicated as one of the most common causes of outbreaks of acute gastroenteritis (AGE) and sporadic acute diarrhea episodes in subjects of any age. In 2016 the World Health Organization stated that the development of a NoV vaccine should be considered an absolute priority. Unfortunately, the development of an effective NoV vaccine has proven extremely difficult, and only in recent years, some preparations have been tested in humans in advanced clinical trials. In this paper, reasons that justify efforts to develop a NoV vaccine, difficulties encountered during NoV vaccine development, and NoV vaccine candidates will be discussed. In recent years, identification of some NoV antigens that alone or in combination with other viral antigens can induce a potentially protective immune response has led to the development of a large series of preparations that seem capable of coping with the problems related to NoV infection. Epidemiological and immunological studies have shown that multivalent vaccines, including both GI and GII NoV, are the only solution to induce sufficiently broad protection. However, even if the road to formulation of an effective and safe NoV vaccine seems to be definitively traced, many problems still need to be solved before the total burden of NoV infections can be adequately controlled. Whether currently available vaccines are able to protect against all the heterologous NoV strains and the variants of the most common serotypes that frequently emerge and cause outbreaks must be defined. Moreover, as performed clinical trials have mainly enrolled adults, it is mandatory to know whether vaccines are effective in all age groups, including younger children. Finally, we must know the immune response of immunocompromised patients and the duration of protection induced by NoV vaccines. Only when all these problems have been solved will it be possible to establish an effective immunization schedule against NoV infection and calculate whether systematic vaccination can be cost effective.
诺如病毒（NoV）被鉴定后，一直被认为是导致任何年龄段人群急性胃肠炎（AGE）暴发和散发性急性腹泻的最常见原因之一。2016 年，世界卫生组织表示，开发诺如病毒疫苗应被视为绝对优先事项。不幸的是，开发有效的诺如病毒疫苗已被证明极其困难，直到近年来，一些制剂才在人类中进行了先进的临床试验测试。本文将讨论开发诺如病毒疫苗的理由、在开发诺如病毒疫苗过程中遇到的困难，以及诺如病毒疫苗的候选物。近年来，鉴定出一些诺如病毒抗原，单独或与其他病毒抗原联合使用，可诱导潜在的保护性免疫反应，这导致了一系列制剂的开发，这些制剂似乎有能力应对与诺如病毒感染相关的问题。流行病学和免疫研究表明，包括 GI 和 GII 诺如病毒在内的多价疫苗是诱导足够广泛保护的唯一解决方案。然而，即使开发有效和安全的诺如病毒疫苗的道路似乎已经明确，在充分控制诺如病毒感染的总负担之前，仍有许多问题需要解决。是否现有的疫苗能够预防所有异源诺如病毒株和经常出现并引起暴发的最常见血清型的变体，这一点仍有待确定。此外，由于进行的临床试验主要纳入了成年人，因此必须了解疫苗在所有年龄段（包括幼儿）是否有效。最后，我们必须了解免疫功能低下患者的免疫反应以及诺如病毒疫苗诱导的保护持续时间。只有当所有这些问题都得到解决后，才有可能建立针对诺如病毒感染的有效免疫接种计划，并计算系统接种疫苗是否具有成本效益。
