Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain; Autonomous University of Madrid, Madrid, Spain.
Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain.
Fish Shellfish Immunol. 2022 Sep;128:419-424. doi: 10.1016/j.fsi.2022.07.039. Epub 2022 Jul 30.
Disease prevention by vaccination is, on economic, environmental and ethical grounds the most appropriate method for pathogen control currently available to the aquaculture sector. However, vaccine administration in aquatic animals faces obvious technical problems not encountered in other land animals. Thus, oral vaccines are highly demanded by the aquaculture sector that requests alternatives to the labor-intensive injectable vaccines that require individual handling of fish, provoking stress-related immunosuppression and handling mortalities. Despite this, most previous attempts to obtain effective oral vaccines have failed both in fish and mammals. This could be a consequence of very restricted tolerance mechanisms in the intestine given the fact that this mucosa is at the frontline upon antigen encounter and has to balance the delicate equilibrium between tolerance and immunity in a microbe rich aquatic environment. In this context, the search for an optimal combination of antigen and adjuvant that can trigger an adequate immune response able to circumvent intestinal tolerance is needed for each pathogen. To this aim, we have explored potential of molecules such as β-glucans, flagellin, CpG and bacterial lipopolysacharide (LPS) as oral adjuvants. For this, we have determined the effects of these adjuvants ex vivo in rainbow trout intestine tissue sections, and in vitro in leucocytes isolated from rainbow trout spleen and intestine. The effects were evaluated by analyzing the levels of transcription of different genes related to the innate and adaptive immune response, as well as evaluating the number of IgM-secreting cells. LPS seems to be the molecule with stronger immunostimulatory potential, and could safely be used as a mucosal adjuvant in rainbow trout. Moreover, the designed strategy provides a fast methodology to screen adjuvants that are suitable for oral vaccination, providing us with valuable information about how the intestinal mucosa is regulated in fish.
疫苗接种预防疾病，从经济、环境和伦理角度来看，是水产养殖部门目前可用于病原体控制的最合适方法。然而，在水生动物中进行疫苗接种面临着明显的技术问题，这些问题在其他陆地动物中并未遇到。因此，水产养殖业强烈要求使用口服疫苗来替代需要对鱼类进行个体处理的、劳动密集型的注射疫苗，因为这种处理方式会引起与应激相关的免疫抑制和处理死亡率。尽管如此，在鱼类和哺乳动物中，大多数先前试图获得有效口服疫苗的尝试都失败了。这可能是由于肠道中的耐受机制非常有限，因为肠道黏膜是抗原接触的第一线，必须在富含微生物的水生环境中平衡耐受和免疫之间的微妙平衡。在这种情况下，需要针对每种病原体寻找最佳的抗原和佐剂组合，以触发能够规避肠道耐受的适当免疫反应。为此，我们探索了β-葡聚糖、鞭毛蛋白、CpG 和细菌脂多糖（LPS）等分子作为口服佐剂的潜力。为此，我们在虹鳟鱼肠组织切片中以及从虹鳟鱼脾脏和肠道分离的白细胞中体外测定了这些佐剂的效果。通过分析与先天和适应性免疫反应相关的不同基因的转录水平以及评估 IgM 分泌细胞的数量来评估效果。LPS 似乎是具有最强免疫刺激潜力的分子，可安全地用作虹鳟鱼的粘膜佐剂。此外，所设计的策略提供了一种快速筛选适合口服疫苗接种的佐剂的方法，为我们提供了有关肠道黏膜在鱼类中如何调节的有价值信息。
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