Virus-like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection.
Virus-like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection.
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DOI：
10.1021/acscentsci.7b00311
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发表时间：
2017-09-27
影响因子：
18.2
通讯作者：
Marques AF
中科院分区：
文献类型：
--
作者：
Moura APV;Santos LCB;Brito CRN;Valencia E;Junqueira C;Filho AAP;Sant'Anna MRV;Gontijo NF;Bartholomeu DC;Fujiwara RT;Gazzinelli RT;McKay CS;Sanhueza CA;Finn MG;Marques AF
分泌的和表面显示的碳水化合物对于许多寄生虫的毒力和生存能力是必不可少的，包括对免疫系统的逃避。我们鉴定了原生动物婴儿利什曼原虫和亚马逊利什曼原虫表面的α-半乳糖三糖表位，这两种原虫分别是内脏利什曼病和皮肤利什曼病的病原体，后者比前者携带更多的α-半乳糖。在C57BL/6α-半乳糖基转移酶基因敲除小鼠模型中，用免疫原性Qβ病毒样颗粒上的多价α-Gal结合物作为疫苗对抗利什曼原虫感染，该模型模仿人类宿主产生高滴度的抗α-Gal抗体。正如预期的那样，与野生型小鼠相比，感染这两种利什曼原虫前鞭毛虫的α-Gal-T基因敲除小鼠的肝脏寄生虫载量显著降低，脾的寄生虫载量略有下降。用Qβ-α-Gal纳米粒免疫基因敲除小鼠可保护小鼠免受利什曼原虫攻击，消除肝脏和脾内寄生虫的感染和增殖。因此，α-Gal表位可被认为是阻断人类皮肤和内脏利什曼病的候选疫苗。利什曼原虫显示免疫原性α-Gal碳水化合物表位。针对这种结构的免疫在模仿人类α-Gal生物化学的小鼠模型中对这些寄生虫提供了保护性免疫。
Secreted and surface-displayed carbohydrates are essential for virulence and viability of many parasites, including for immune system evasion. We have identified the α-Gal trisaccharide epitope on the surface of the protozoan parasites Leishmania infantum and Leishmania amazonensis, the etiological agents of visceral and cutaneous leishmaniasis, respectively, with the latter bearing larger amounts of α-Gal than the former. A polyvalent α-Gal conjugate on the immunogenic Qβ virus-like particle was tested as a vaccine against Leishmania infection in a C57BL/6 α-galactosyltransferase knockout mouse model, which mimics human hosts in producing high titers of anti-α-Gal antibodies. As expected, α-Gal-T knockout mice infected with promastigotes of both Leishmania species showed significantly lower parasite load in the liver and slightly decreased levels in the spleen, compared with wild-type mice. Vaccination with Qβ–α-Gal nanoparticles protected the knockout mice against Leishmania challenge, eliminating the infection and proliferation of parasites in the liver and spleen as probed by qPCR. The α-Gal epitope may therefore be considered as a vaccine candidate to block human cutaneous and visceral leishmaniasis. Leishmania protozoa display the immunogenic α-Gal carbohydrate epitope. Immunization against this structure confers protective immunity against these parasites in a mouse model that mimics human α-Gal biochemistry.
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影响因子：
3.7
作者：
MCCOY, JP;VARANI, J;GOLDSTEIN, IJ
通讯作者：
GOLDSTEIN, IJ
影响因子：
5.3
作者：
Nascimento Brito, Carlos Ramon;Mckay, Craig S.;Marques, Alexandre Ferreira
通讯作者：
Marques, Alexandre Ferreira
影响因子：
3
作者：
Rempel, BP;Winter, HC;Hindsgaul, O
通讯作者：
Hindsgaul, O
DOI：
10.1084/jem.185.12.2061
发表时间：
1997-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Bates PA
通讯作者：
Bates PA