Conner M E, Matson D O, Estes M K
Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030.
Curr Top Microbiol Immunol. 1994;185:285-337. doi: 10.1007/978-3-642-78256-5_10.
The development of a successful rotavirus vaccine is a complex problem. Our review of rotavirus vaccine development shows that many challenges remain, and priorities for future studies need to be established. For example, the evaluation of administration of a vaccine with OPV or breast milk might receive less emphasis until a vaccine is made that shows clear efficacy against all virus serotypes. Samples remaining from previous trials should be analyzed to determine epitope-specific serum and coproantibody responses to clarify why only some trials were successful. Detailed evaluation of the antigenic properties of the viruses circulating and causing illness in vaccinated children also should be performed for comparisons with the vaccine strains. In future trials, sample collection should include monitoring for asymptomatic infections and cellular immune responses should be analyzed. The diversity of rotavirus serotype distribution must be monitored before, during, and after a trial in the study population and placebo recipients must be matched carefully to vaccine recipients. Epidemiologic and molecular studies should be expanded to document, or disprove, the possibility of animal to human rotavirus transmission, because, if this occurs, vaccine protection may be more difficult in those areas of the world where cohabitation with animals occurs. We also need to have an accurate assessment of the rate of protection that follows natural infections. Is it realistic to try to achieve 90% protective efficacy with a vaccine if natural infections with these enteric pathogens only provide 60% or 70% protection? Subunit vaccines should be considered to be part of vaccine strategies, especially if maternal antibody interferes with the take of live vaccines. The constraints on development of new vaccines are not likely to come from molecular biology. The challenge remains whether the biology and immunology of rotavirus infections can be understood and exploited to permit effective vaccination. Recent advances in developing small animal models for evaluation of vaccine efficacy should facilitate future vaccine development and understanding of the protective immune response(s) (Ward et al. 1990b; Conner et al. 1993).
研发一种成功的轮状病毒疫苗是一个复杂的问题。我们对轮状病毒疫苗研发的综述表明，仍存在许多挑战，需要确定未来研究的重点。例如，在研发出对所有病毒血清型均显示出明确疗效的疫苗之前，对同时接种口服脊髓灰质炎疫苗（OPV）或母乳的疫苗接种情况的评估可能不会受到太多重视。应分析先前试验剩余的样本，以确定表位特异性血清和粪便抗体反应，从而阐明为何只有部分试验取得成功。还应对接种疫苗儿童中传播并致病的病毒的抗原特性进行详细评估，以便与疫苗株进行比较。在未来的试验中，样本采集应包括对无症状感染的监测，并且应分析细胞免疫反应。在研究人群中进行试验之前、期间和之后，必须监测轮状病毒血清型分布的多样性，并且安慰剂接受者必须与疫苗接受者仔细匹配。应扩大流行病学和分子研究，以证实或反驳动物向人类传播轮状病毒的可能性，因为如果发生这种情况，在世界上人与动物同居的地区，疫苗保护可能会更加困难。我们还需要准确评估自然感染后的保护率。如果这些肠道病原体的自然感染仅提供60%或70%的保护，那么试图通过疫苗实现90%的保护效力是否现实？应考虑将亚单位疫苗作为疫苗策略的一部分，尤其是在母体抗体干扰活疫苗接种的情况下。新疫苗研发的限制不太可能来自分子生物学。挑战仍然在于是否能够理解和利用轮状病毒感染的生物学和免疫学特性，从而实现有效的疫苗接种。在开发用于评估疫苗效力的小动物模型方面的最新进展，应有助于未来的疫苗研发以及对保护性免疫反应的理解（Ward等人，1990b；Conner等人，1993）。
