血吸虫病在中国和菲律宾仍然是一种严重的人畜共患疾病。水牛和牛占传播的大部分。水牛疫苗接种被认为是降低疾病患病率的关键策略。以前,我们发现用SjC23或SjCTPI质粒DNA疫苗接种水牛,诱导50%的疗效来攻击感染。这里,我们评估了几个参数,以确定我们是否可以开发出保持三剂量疫苗效力的两剂量疫苗。我们进行了四个试验评估:(1)实验室生产与GLP级疫苗,(2)改变prime和boost之间的时间,(3)IL-12佐剂的影响,和(4)双剂量异源(DNA-蛋白质)初免-加强。我们发现DNA疫苗的来源并不重要,也没有增加prime和boost之间的间隔。IL-12质粒的消除降低了同源DNA-DNA疫苗的效力。一个主要的发现是,异源初免加强提高了疫苗的功效,结合两种抗原的初免-加强方案可使成虫减少55%,肝卵减少53%。接种水牛产生疫苗特异性抗体应答。这些试验表明,使用双剂量方案可以实现针对血吸虫的高效疫苗接种。没有佐剂与蛋白质加强一起使用,应评估向蛋白质中添加佐剂以进一步提高功效的潜力。这些结果表明,使用这两种血吸虫疫苗可以成为减少亚洲血吸虫病传播的综合控制策略的一部分。
Schistosomiasis remains a serious zoonotic disease in China and the Philippines. Water buffalo and cattle account for the majority of transmission. Vaccination of water buffalo is considered a key strategy to reduce disease prevalence. Previously, we showed that vaccination of water buffalo with
SjC23 or SjCTPI plasmid DNA vaccines, induced 50% efficacy to challenge infection. Here, we evaluated several parameters to determine if we can develop a two dose vaccine that maintains the efficacy of the three dose vaccine. We performed four trials evaluating: (1) lab produced vs. GLP grade vaccines, (2) varying the time between prime and boost, (3) the influence of an IL-12 adjuvant, and (4) a two dose heterologous (DNA-protein) prime-boost. We found the source of the DNA vaccines did not matter, nor did increasing the interval between prime and boost. Elimination of the IL-12 plasmid lowered homologous DNA-DNA vaccine efficacy. A major finding was that the heterologous prime boost improved vaccine efficacy, with the prime-boost regimen incorporating both antigens providing a 55% reduction in adult worms and 53% reduction in liver eggs. Vaccinated buffalo produced vaccine-specific antibody responses. These trials suggest that highly effective vaccination against schistosomes can be achieved using a two dose regimen. No adjuvants were used with the protein boost, and the potential that addition of adjuvant to the protein boost to further increase efficacy should be evaluated. These results suggest that use of these two schistosome vaccines can be part of an integrated control strategy to reduce transmission of schistosomiasis in Asia.