Vaccination against filarial nematodes with irradiated larvae provides long-term protection against the third larval stage but not against subsequent life cycle stages
Vaccination against filarial nematodes with irradiated larvae provides long-term protection against the third larval stage but not against subsequent life cycle stages
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DOI：
10.1016/j.ijpara.2006.04.013
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Bain, Odile
中科院分区：
文献类型：
--
作者：
Babayan, Simon A.;Attout, Tarik;Bain, Odile
人类丝虫病的可持续控制将从有效疫苗的开发中受益匪浅。为实验动物接种疫苗的能力表明，这一目标是可能的，蠕虫负担减少了70%以上。然而，在实验性疫苗接种中，挑战通常在免疫阶段后2周进行，因此，由于持续的炎症，获得的保护很可能是有偏见的。使用Sitomosoidessigmodontis小鼠模型，我们将照射幼虫免疫和完全感染L3攻击之间的时间延长到5个月。获得了显著的保护作用(54-58%)，并在P.I.的10天内观察到减少了蠕虫负担。目标发育阶段是L3，因为正如先前在短期方案中所显示的那样，线虫一旦到达接种疫苗的小鼠的胸膜腔就没有死亡。然而，接种疫苗的小鼠的幼虫发育速度快于初次感染的小鼠。分别于激发前、激发后6h至34d进行免疫学评估。样本取自接种幼虫的皮下组织、幼虫迁徙通过的淋巴结和建立幼虫的胸腔。尽管在攻击前接种疫苗的小鼠皮下组织中的嗜酸性粒细胞很少，但仍然存在。免疫和攻击小鼠的细胞因子和特异性抗体的产生具有L3特异性和Th2偏向性，大大超过了初发感染小鼠的反应。Th2应答的增强可能解释了丝虫在免疫小鼠中发展更快的原因。因此，长期疫苗接种方案产生了强烈的记忆反应，导致了显著但不完全的保护，仅限于感染幼虫阶段，这表明需要替代的疫苗接种策略。(C)2006澳大利亚寄生虫学协会。爱思唯尔有限公司出版。版权所有。
Sustainable control of human filariasis would benefit enormously from the development of an effective vaccine. The ability to vaccinate experimental animals, with reductions in worm burden of over 70%, suggests this aim is possible. However, in experimental vaccinations the challenge is usually administered 2 weeks after the immunisation phase and thus the protection obtained is likely to be biased by persisting inflammation. Using the murine model Litomosoides sigmodontis, we increased the time between immunisation with irradiated larvae and challenge with fully infective L3 to 5 months. Significant protection was achieved (54-58%) and the reduced worm burden was observed by 10 days p.i. The developmental stage targeted was the L3, since no nematodes died once they reached the pleural cavity of vaccinated mice, as has been previously shown in short-term protocols. However, larval developmental rate was faster in vaccinated than in primary-infected mice. Immunological assessments were made prior to challenge and then from 6 h to 34 days post-challenge. Samples were taken from the subcutaneous tissue where the larvae were inoculated, the lymph nodes through which they migrate and the pleural cavity in which they establish. Eosinophils were still present although scarce in the subcutaneous tissue of vaccinated mice before challenge. Cytokine and specific antibody production of vaccinated and challenged mice were L3-specific and Th2-biased and greatly exceeded the response of primary-infected mice. The heightened Th2 response may explain the faster development of the filarial worms in vaccinated mice. Thus, long-term vaccination protocols generated a strong memory response that led to significant but incomplete protection that was limited to the infective larval stage suggesting alternative vaccination strategies are needed. (c) 2006 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.