Based on the status of oral vaccine

Based on the status of oral vaccines in humans and veterinary species, there is no doubt that the generation of safe and efficacious oral vaccines is among one of the most difficult tasks of immunologists. This is illustrated by the very limited number or oral vaccines approved for use in humans and the slightly larger number approved for use in poultry, pigs and cattle. In this respect fish are not lagging much behind, with 5 oral vaccines available on the market. These vaccines however, are against only a very limited number of pathogens and are available for an even smaller number of fish species. When considering the vast diversity of cultured fish species and their pathogens, the current oral vaccines are by far insufficient to fulfil the market requirements. Such species diversity is in fact larger than the diversity in species and pathogens faced by for example the poultry or cattle vaccine industry.

Nonetheless, fish oral vaccine development can greatly profit from the progress made on human and veterinary oral vaccines. For example, the use of live vectors, e.g adenoviruses, or a more rational attenuation of enteric pathogens, e.g E. tarda or V. anguillarum, as well as the combination of weak oral antigens with strong mucosal adjuvants, e.g enterotoxins, leaves a vast number of combinations that have not been fully exploited in fish vaccine development. Fish mucosal immunology, despite the large body of work performed in the last 30 years, is still in its infancy, mostly due to the great heterogeneity in teleost species. Nevertheless, the discovery of new players in fish mucosal immunity within the last 5–10 years, including IgT or M-like sampling cells, keeps the field of mucosal immunology and vaccinology a dynamic and developing area. The possibility to specifically target M-like cells or putative APCs in the fish gut is becoming a viable option in fish vaccine delivery as well. This is being realized through the great advances in gene discovery and the several genome sequencing initiatives for several fish species and their pathogens. The bottleneck will of course be the functional characterization of most of the novel genes and the translation of this fundamental knowledge into practical applications linked to vaccine development. Molecular traceable and genetically modifiable models such as transgenic or mutant zebrafish can support and accelerate fish vaccine development as much as other animal models have helped the human and veterinary field. Information on host mucosal responses, together with insights in how fish gut microbiota might influence the response to oral vaccination is increasing at a rapid paste. This information will be essential to design strategies aimed at breaking mucosal tolerance while preventing inflammation for a greater variety of fish species. Finally, collaborations between academia, industrial partners and farmers will be instrumental to produce safe and efficacious vaccines for most commercially relevant fish species.

結果 (中文) 1:

基于在人类和兽医物种的口服疫苗的研究现状，毫无疑问，代的安全和有效的口服疫苗是免疫学家最困难的任务之一。这被说明数量非常有限或口服疫苗批准用于人类和批准用于家禽、 猪和牛的稍大一些。在这方面鱼不滞后远远落后，与市场上现有的 5 口服疫苗。然而，这些疫苗反对只有非常有限的病原体和供鱼类甚至小数量。当考虑到广大的养殖的鱼类物种多样性和其病原体，当前口服疫苗是远远不足以满足市场要求。这种物种多样性事实上大于在物种多样性和病原体面临的例如家禽或牛的疫苗行业。Nonetheless, fish oral vaccine development can greatly profit from the progress made on human and veterinary oral vaccines. For example, the use of live vectors, e.g adenoviruses, or a more rational attenuation of enteric pathogens, e.g E. tarda or V. anguillarum, as well as the combination of weak oral antigens with strong mucosal adjuvants, e.g enterotoxins, leaves a vast number of combinations that have not been fully exploited in fish vaccine development. Fish mucosal immunology, despite the large body of work performed in the last 30 years, is still in its infancy, mostly due to the great heterogeneity in teleost species. Nevertheless, the discovery of new players in fish mucosal immunity within the last 5–10 years, including IgT or M-like sampling cells, keeps the field of mucosal immunology and vaccinology a dynamic and developing area. The possibility to specifically target M-like cells or putative APCs in the fish gut is becoming a viable option in fish vaccine delivery as well. This is being realized through the great advances in gene discovery and the several genome sequencing initiatives for several fish species and their pathogens. The bottleneck will of course be the functional characterization of most of the novel genes and the translation of this fundamental knowledge into practical applications linked to vaccine development. Molecular traceable and genetically modifiable models such as transgenic or mutant zebrafish can support and accelerate fish vaccine development as much as other animal models have helped the human and veterinary field. Information on host mucosal responses, together with insights in how fish gut microbiota might influence the response to oral vaccination is increasing at a rapid paste. This information will be essential to design strategies aimed at breaking mucosal tolerance while preventing inflammation for a greater variety of fish species. Finally, collaborations between academia, industrial partners and farmers will be instrumental to produce safe and efficacious vaccines for most commercially relevant fish species.

結果 (中文) 3:

基于对人类和动物植物口服疫苗的现状，毫无疑问，安全有效的口服疫苗是免疫学中的一个最困难的任务的生成。这是说明了非常有限的数量或口服疫苗批准用于在人类和略大一些批准用于家禽，猪和牛的数量。在这方面，鱼并没有落后太多，在市场上可用的5个口服疫苗。然而，这些疫苗，只对一个非常有限的病原体数量，可用于一个甚至更小的数量的鱼。当考虑到巨大的多样性的养殖鱼类和他们的病原体，目前的口服疫苗是远远不够的，以满足市场的要求。这种物种多样性实际上是大于物种和病原体所面临的例如家禽或牛疫苗行业的多样性。然而，鱼口服疫苗的开发可以大大受益于人类和兽用口服疫苗的进展。例如，使用活的载体，如腺病毒，或更合理的肠道病原体衰减，例如大肠菌和鳗弧菌，以及弱口服抗原具有较强的粘膜免疫佐剂，组合如肠毒素，留下大量未充分利用的组合鱼类疫苗的发展。鱼的粘膜免疫，尽管在过去的30年中的大量工作，尚处于起步阶段，主要是由于在硬骨鱼类的巨大异质性。然而，在鱼类粘膜免疫在过去5–10年新玩家的发现，包括IGT或M-细胞取样，保持粘膜免疫学和疫苗学的一个动态的、发展的领域。可能的具体目标在鱼肠道M细胞或假定的APC成为鱼疫苗交付作为一个可行的选择。这是通过基因发现的巨大进步和几种鱼类及其病原体的几种基因组测序计划来实现的。的瓶颈当然是大多数的新基因的功能特性和这一基本知识转化为实际应用与疫苗开发的翻译。分子可追溯的基因修改的模型，如转基因或突变的斑马鱼可以支持和促进鱼类疫苗的发展为其他的动物模型有助于人类和动物界一样。对宿主的粘膜免疫应答信息，连同见解鱼类肠道菌群可能影响口服疫苗的反应是快速粘贴增加。这些信息将是必不可少的设计策略，旨在打破粘膜耐受性，同时防止炎症更大的品种的鱼。最后，学术界，工业合作伙伴和农民之间的合作将有助于生产最重要的商业相关的鱼类的安全和有效的疫苗。