Begg D J, Dhungyel O, Naddi A, Dhand N K, Plain K M, de Silva K, Purdie A C, Whittington R J
School of Veterinary Science, Faculty of Science, The University of Sydney, NSW, Australia.
Heliyon. 2019 Jun 18;5(6):e01911. doi: 10.1016/j.heliyon.2019.e01911. eCollection 2019 Jun.
Johne's disease (JD) is a chronic enteritis caused by subspecies (MAP). Current commercial vaccines are effective in reducing the occurrence of clinical disease although vaccinated animals can still become infected and transmit MAP. Many vaccinated sheep develop severe injection site lesions. In this study a range of adjuvants (Montanide ISA 50V, ISA 50V2, ISA 61VG, ISA 70 M VG, ISA 71 VG, ISA 201 VG and Gel 01 PR) formulated with heat-killed MAP were tested to determine the incidence of injection site lesions and the types of immune profiles generated in sheep. All the novel formulations produced fewer injection site lesions than a commercial vaccine (Gudair®). The immune profiles of the sheep differed between treatment groups, with the strength of the antibody and cell mediated immune responses being dependant on the adjuvant used. One of the novel vaccines resulted in a reduced IFN-γ immune response when a second "booster" dose was administered. These findings have significance for JD vaccine development because it may be possible to uncouple protective immunity from excessive tissue reactivity, and apparently poorly immunogenic antigens may be re-examined to determine if an appropriate immune profile can be established using different adjuvants. It may also be possible to formulate vaccines that produce targeted immunological profiles suited to protection against other pathogens, i.e. those for which a bias towards cellular or humoral immunity would be advantageous based on understanding of pathogenesis.
副结核(JD)是由副结核分枝杆菌亚种(MAP)引起的一种慢性肠炎。目前的商业疫苗在降低临床疾病的发生率方面是有效的,尽管接种疫苗的动物仍可能被感染并传播MAP。许多接种疫苗的绵羊会出现严重的注射部位病变。在本研究中,测试了一系列与热灭活MAP配制的佐剂(Montanide ISA 50V、ISA 50V2、ISA 61VG、ISA 70 M VG、ISA 71 VG、ISA 201 VG和Gel 01 PR),以确定绵羊注射部位病变的发生率以及所产生的免疫谱类型。所有新配方产生的注射部位病变都比商业疫苗(Gudair®)少。不同治疗组绵羊的免疫谱有所不同,抗体和细胞介导免疫反应的强度取决于所使用的佐剂。当给予第二剂“加强”剂量时,其中一种新型疫苗导致IFN-γ免疫反应降低。这些发现对JD疫苗的开发具有重要意义,因为有可能将保护性免疫与过度的组织反应性分开,并且可能需要重新审视明显免疫原性较差的抗原,以确定是否可以使用不同的佐剂建立适当的免疫谱。还可能配制出产生适合针对其他病原体的靶向免疫谱的疫苗,即基于对发病机制的理解,对细胞免疫或体液免疫有偏向性会更有利的那些病原体。