Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.
Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.
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来自整个利什曼原虫抗原的鼻内疫苗可提供保护并诱导针对内脏利什曼病的特定免疫反应。
DOI：
10.1371/journal.pntd.0009627
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发表时间：
2021-08
影响因子：
3.8
通讯作者：
Cojean S
中科院分区：
文献类型：
--
作者：
Helou DG;Mauras A;Fasquelle F;Lanza JS;Loiseau PM;Betbeder D;Cojean S
内脏利什曼病是一种原虫病，在发展中国家具有很高的病死率。虽然药物管道正在不断改进，但可用的治疗方法价格昂贵，危及生命的副作用并不罕见。此外，目前还没有一种经批准的预防人类利什曼病的疫苗。利用杜氏利什曼原虫前鞭毛体（LdAg）的全抗原，我们研究了一种新的无佐剂疫苗策略的保护潜力。在感染前通过皮内或鼻内途径对小鼠进行LdAg免疫接种，可降低主要受影响内脏器官（包括肝脏、脾脏和骨髓）中的寄生虫负荷。有趣的是，鼻内途径比皮内途径更有效，导致更好的寄生虫清除和显著诱导适应性免疫细胞，特别是辅助和细胞毒性T细胞。利什曼原虫抗原的体外再刺激实验导致脾细胞显著分泌IFN-γ;因此，例证了适应性免疫应答的特异性。为了改善粘膜递送和我们的疫苗策略的免疫原性方面，我们使用携带抗原的基于多糖的纳米颗粒（NP）。NP-LdAg制剂被树突状细胞显著摄取并诱导其体外成熟，如通过CD 80、CD 86和MHC II的表达增加所揭示的。在我们的实验时间轴中，用NP-LdAg鼻内免疫并没有改善寄生虫清除;然而，它确实增加了脾脏中效应和记忆T辅助细胞的百分比，这表明潜在的长期记忆诱导。总之，本研究提供了一种简单且具有成本效益的内脏利什曼病疫苗策略，该策略基于通过鼻内途径给予LdAg，可适用于其他寄生虫病。内脏利什曼病是一种被忽视的热带疾病，由特定种类的利什曼原虫寄生虫引起，影响内脏器官，包括脾脏，肝脏和骨髓。感染阶段称为前鞭毛体，通过白蛉叮咬传播到宿主皮肤。内脏利什曼病通常与贫穷和发展中国家的高死亡率有关，缺乏适当的卫生援助。此外，治疗是昂贵的，而没有批准的疫苗存在，以防止感染和避免疾病爆发。这项研究提出了一种负担得起的和无毒素的疫苗配方，从总裂解物的前鞭毛体。通过鼻内途径施用疫苗确保了从感染的实验小鼠的内脏中显著清除利什曼原虫寄生虫。特别地，已知非侵入性的鼻内途径在诱导针对寄生虫的感染形式的充分免疫应答方面是有效的。现在需要进一步的研究来改进这种预防性疫苗，并因此为有前途的翻译方法提供基础。
Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases. Visceral leishmaniasis is a neglected tropical disease caused by specific species of Leishmania parasites that affect internal organs including spleen, liver, and bone marrow. The infective stage called promastigote, is transmitted into the host skin via sandfly bites. Visceral leishmaniasis is usually associated with high mortality rate in poor and developing countries, lacking proper health assistance. Moreover, treatments are expensive while no approved vaccines exist to prevent infection and avoid disease outbreaks. This study suggests an affordable and adjuvant-free vaccine formulation made from the total lysate of promastigotes. Vaccine administration via the intranasal route, ensures a remarkable clearance of Leishmania parasites from the internal organs of infected experimental mice. In particular, intranasal route known to be not invasive, is efficient in inducing adequate immune response against the infective form of the parasite. Further studies are now required to improve this prophylactic vaccine and provide therefore the basis for a promising translational approach.
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影响因子：
3.2
作者：
Ejazi, Sarfaraz Ahmad;Ghosh, Smriti;Ali, Nahid
通讯作者：
Ali, Nahid
影响因子：
3.8
作者：
Cojean, Sandrine;Nicolas, Valerie;Lievin-Le Moal, Vanessa
通讯作者：
Lievin-Le Moal, Vanessa
DOI：
10.1590/s0074-02762010000600002
发表时间：
2010-09-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
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作者：
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通讯作者：
Vieira, Leda Quercia
影响因子：
4.3
作者：
Banerjee, Antara;Bhattacharya, Parna;Nakhasi, Hira L.
通讯作者：
Nakhasi, Hira L.
影响因子：
14
作者：
Dimier-Poisson, Isabelle;Carpentier, Rodolphe;Betbeder, Didier
通讯作者：
Betbeder, Didier