Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia after challenge infection by inhibition of filarial embryogenesis.
Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia after challenge infection by inhibition of filarial embryogenesis.
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DOI：
10.1371/journal.pntd.0001558
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发表时间：
2012
影响因子：
3.8
通讯作者：
Specht S
中科院分区：
文献类型：
--
作者：
Ziewer S;Hübner MP;Dubben B;Hoffmann WH;Bain O;Martin C;Hoerauf A;Specht S
淋巴丝虫病和盘尾丝虫病是两种由寄生蠕虫介导的慢性疾病，可造成长期残疾和严重的社会经济问题。丝虫通过吸血蚊子传播，吸血蚊子从受感染的宿主身上摄取第一阶段的幼虫，并在其成熟后进入感染阶段后将其运送到新宿主。在病媒控制项目结束后，疾病控制主要依赖于大规模药物给药，这些药物主要对第一阶段幼虫有效，需要多年的年度/半年给药。因此，迫切需要替代治疗方法，即其他有效的药物或疫苗。使用Litomosoides sigmodontis小鼠模型的丝虫病，我们证明，免疫与微丝蚴一起佐剂明矾预防小鼠从发展高微丝蚴血症后挑战感染。免疫在外周血和胸膜腔中实现了70%至100%的保护，并且进一步强烈降低了保持微丝蚴血症的小鼠中的微丝蚴负荷。保护作用与宫内丝虫胚胎发育受损、局部和全身微丝蚴特异性宿主IgG以及感染部位宿主细胞分泌IFN-γ有关。此外，免疫显着降低成虫负担。我们的研究结果提出了一个工具，以了解疫苗诱导保护的免疫学基础，以开发一种基于微丝蚴的疫苗，减少成虫的负担，防止微丝蚴血症，一个强大的武器，阻止丝虫病的传播。淋巴丝虫病是由蚊子传播的寄生蠕虫引起的，需要吸收幼虫并分布到宿主的血液中。超过1.2亿人被感染，其中约30%的人患有临床症状。减少传播目前取决于大规模药物管理，这在过去几年中大大降低了传播率。然而，尽管反复进行了几轮管理，但在流行地区并没有完全消除传播。在一些受感染的个体中，免疫系统可以部分控制寄生虫，使得一部分受感染的个体保持微丝蚴阴性，尽管存在蠕虫。因此，必须存在能够防治微丝蚴血症的机制。确定这些机制将有助于设计针对传播微丝蚴阶段疾病的疫苗。使用Litomosoides sigmodontis小鼠模型的丝虫病研究，我们显示了一个成功的免疫对血液循环幼虫阶段，负责节肢动物依赖的疾病传播。微丝蚴血症减少与蠕虫胚胎发育受损、全身和局部微丝蚴特异性宿主IgG以及感染部位宿主细胞分泌IFN-γ相关。这些结果为开发基于微丝蚴的疫苗带来了希望，这是消除丝虫病的关键一步。
Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines. Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden. Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis. Lymphatic filariasis is caused by parasitic filarial worms that are transmitted by mosquitoes, requiring uptake of larvae and distribution into the blood of the host. More than 120 million people are infected and about 30% of these individuals suffer from clinical symptoms. Reduction in transmission currently depends on mass drug administration, which has significantly reduced transmission rates over the past years. However, despite repetitive rounds of administration, transmission has not been eliminated completely from endemic areas. In some infected individuals the immune system can partially control the parasite, such that a proportion of infected individuals remain microfilaria-negative, despite the presence of adult worms. Therefore mechanisms must exist that are able to combat microfilaraemia. Identifying such mechanisms would help to design vaccines against disease transmitting microfilarial stages. Using the Litomosoides sigmodontis murine model of filariasis research we show a successful immunization against the blood-circulating larval stage that is responsible for arthropod-dependent transmission of the disease. Reduced microfilaraemia was associated with impairment of worm embryogenesis, with systemic and local microfilarial-specific host IgG and with IFN-γ secretion by host cells at the site of infection. These results raise hope for developing a microfilariae-based vaccine, being a pivotal step towards eradicating filariasis.
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影响因子：
3.1
作者：
AlQaoud, KM;Taubert, A;Hoerauf, A
通讯作者：
Hoerauf, A
影响因子：
5.5
作者：
Dabir, Snehal;Dabir, Pankaj;Reddy, M. V. R.
通讯作者：
Reddy, M. V. R.
影响因子：
5.5
作者：
Dixit, S.;Gaur, R. L.;Murthy, P. K.
通讯作者：
Murthy, P. K.
DOI：
10.1016/0035-9203(81)90046-8
发表时间：
1981-01-01
影响因子：
2.2
作者：
HAAS, B;WENK, P
通讯作者：
WENK, P
影响因子：
2.1
作者：
CHANDRASHEKAR, R;RAO, UR;SUBRAHMANYAM, D
通讯作者：
SUBRAHMANYAM, D