Center for Tropical Medicine and Infectious Diseases, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
Front Immunol. 2021 Feb 23;11:578715. doi: 10.3389/fimmu.2020.578715. eCollection 2020.
Asiatic schistosomiasis caused by is a neglected tropical disease resulting in significant morbidity to both humans and animals - particularly bovines - in endemic areas. Infection with this parasite leads to less healthy herds, causing problems in communities which rely on bovines for farming, milk and meat production. Additionally, excretion of parasite eggs in feces perpetuates the life cycle and can lead to human infection. We endeavored to develop a minimally purified, inexpensive, and effective vaccine based on the 80 kDa large subunit of the calcium activated neutral protease (calpain) from (Sj-p80). Here we describe the production of veterinary vaccine-grade Sj-p80 at four levels of purity and demonstrate in a pilot study that minimally purified antigen provides protection against infection in mice when paired with a low-cost veterinary adjuvant, Montanide™ ISA61 VG. Preliminary data demonstrate that the vaccine is immunogenic with robust antibody titers following immunization, and vaccination resulted in a reduction of parasite eggs being deposited in the liver (23.4-51.4%) and intestines (1.9-55.1%) depending on antigen purity as well as reducing the ability of these eggs to hatch into miracidia by up to 31.6%. We therefore present Sj-p80 as a candidate vaccine antigen for Asiatic schistosomiasis which is now primed for continued development and testing in bovines in endemic areas. A successful bovine vaccine could play a major role in reducing pathogen transmission to humans by interrupting the parasitic life cycle and improving quality of life for people living in endemic countries.
由 引起的亚洲血吸虫病是一种被忽视的热带病,在流行地区给人类和动物(尤其是牛)带来了严重的发病率。感染这种寄生虫会导致牛群健康状况不佳,给依赖牛群从事农业、牛奶和肉类生产的社区带来问题。此外,寄生虫卵在粪便中的排泄会使生命周期永久化,并可能导致人类感染。我们努力开发了一种基于 80 kDa 钙激活中性蛋白酶(钙蛋白酶)大亚基的最小纯化、廉价且有效的疫苗 (Sj-p80)。在这里,我们描述了兽医疫苗级别的 Sj-p80 在四个纯度水平上的生产,并在一项初步研究中表明,当与低成本兽医佐剂 Montanide™ ISA61 VG 配对时,最小纯化的抗原可提供针对小鼠感染的保护。初步数据表明,该疫苗具有免疫原性,免疫后可产生强烈的抗体滴度,接种疫苗可减少寄生虫卵在肝脏(23.4-51.4%)和肠道(1.9-55.1%)中的沉积,具体取决于抗原纯度,同时还可将这些卵孵化成毛蚴的能力降低多达 31.6%。因此,我们提出 Sj-p80 作为亚洲血吸虫病的候选疫苗抗原,现已准备好继续在流行地区的牛中进行开发和测试。成功的牛用疫苗可以通过中断寄生虫生命周期和提高流行国家人民的生活质量,在减少病原体向人类传播方面发挥重要作用。