当生物安全措施无法遏制病原体时,疫苗接种是保护鱼类免受病毒性疾病侵害的最佳形式。基于活的减毒病毒的疫苗似乎对于针对具有挑战性的病原体如鲤科疱疹病毒3的疫苗接种最有效。然而,这些疫苗如何有效地保护鱼类免受由致上皮性CyHV-3引起的致命疾病的影响,以及在水生环境中,非直接保护皮肤或g的完整性和功能的哪些方面仍然存在知识空白。为了阐明保护的一些要素,在不存在或存在鲤鱼β-防御素1、2和3的混合物作为佐剂的情况下,使用双缺失疫苗病毒KHV-TΔDUT/TK对鲤鱼进行了CyHV-3疫苗接种。疫苗接种引起的边缘临床症状,低病毒载量和免疫鱼中cd4,cd8和igm基因表达的轻微上调,而血清的中和活性从疫苗接种后14天(dpv)上升。CyHV-3的攻击感染在未接种疫苗的鲤鱼中引起了80-100%死亡率的严重疾病,在接种疫苗的鲤鱼中,没有死亡记录,皮肤中的病毒载量降低了>1000倍,ill和肾.组织学分析显示皮肤病理变化最强,完全破坏未接种鲤鱼的表皮。在未接种疫苗的鱼的皮肤中,T和B细胞反应严重下调,炎症和应激反应在攻击时增加,而接种疫苗的鱼增加了中性粒细胞,T和B细胞反应。皮肤屏障元素的破坏(紧密和粘附连接,桥粒,粘蛋白)导致皮肤细菌负荷的不受控制的增加,这很可能加剧了炎症和病理。使用减毒活疫苗,我们能够证明中性粒细胞增加,T和B细胞反应提供对CyHV-3感染的保护,并导致皮肤完整性的保护,这有助于在水生环境中成功预防其他病原体,这些病原体会促进未接种疫苗的鲤鱼的疾病发展。
Vaccination is the best form of protecting fish against viral diseases when the pathogen cannot be contained by biosecurity measures. Vaccines based on live attenuated viruses seem to be most effective for vaccination against challenging pathogens like Cyprinid herpesvirus 3. However, there are still knowledge gaps how these vaccines effectively protect fish from the deadly disease caused by the epitheliotropic CyHV-3, and which aspects of non-direct protection of skin or gill integrity and function are important in the aquatic environment. To elucidate some elements of protection, common carp were vaccinated against CyHV-3 using a double deletion vaccine virus KHV-T ΔDUT/TK in the absence or presence of a mix of common carp beta-defensins 1, 2 and 3 as adjuvants. Vaccination induced marginal clinical signs, low virus load and a minor upregulation of cd4, cd8 and igm gene expression in vaccinated fish, while neutralisation activity of blood serum rose from 14 days post vaccination (dpv). A challenge infection with CyHV-3 induced a severe disease with 80-100% mortality in non-vaccinated carp, while in vaccinated carp, no mortality was recorded and the virus load was >1,000-fold lower in the skin, gill and kidney. Histological analysis showed strongest pathological changes in the skin, with a complete destruction of the epidermis in non-vaccinated carp. In the skin of non-vaccinated fish, T and B cell responses were severely downregulated, inflammation and stress responses were increased upon challenge, whereas vaccinated fish had boosted neutrophil, T and B cell responses. A disruption of skin barrier elements (tight and adherence junction, desmosomes, mucins) led to an uncontrolled increase in skin bacteria load which most likely exacerbated the inflammation and the pathology. Using a live attenuated virus vaccine, we were able to show that increased neutrophil, T and B cell responses provide protection from CyHV-3 infection and lead to preservation of skin integrity, which supports successful protection against additional pathogens in the aquatic environment which foster disease development in non-vaccinated carp.