Virus-like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection,ACS Central Science

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Virus-like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection
ACS Central Science ( IF 12.7 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1021/acscentsci.7b00311
Anna Paula V. Moura ₁ , Luiza C. B. Santos ₁ , Carlos Ramon Nascimento Brito ₁ , Edward Valencia ₁ , Caroline Junqueira ₂ , Adalberto A. P. Filho ₁ , Mauricio R. V. Sant’Anna ₁ , Nelder F. Gontijo ₁ , Daniella C. Bartholomeu ₁ , Ricardo T. Fujiwara ₁ , Ricardo T. Gazzinelli ₁ , Craig S. McKay ₃ , Carlos A. Sanhueza ₃ , M. G. Finn ₃ , Alexandre Ferreira Marques ₁

Affiliation

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.

中文翻译：

用于预防利什曼原虫感染的α-Gal碳水化合物的病毒样颗粒展示

分泌和表面展示的碳水化合物对于许多寄生虫的毒性和生存力至关重要，包括逃避免疫系统。我们已经确定了原生动物寄生虫婴儿利什曼原虫和亚马逊利什曼原虫的病原体表面上的α-Gal三糖表位，它们分别是内脏和皮肤利什曼病的病原体，后者携带的α-Gal量比前者大。在C57BL / 6α-半乳糖基转移酶敲除小鼠模型中测试了免疫原性Qβ病毒样颗粒上的多价α-Gal偶联物作为抗利什曼原虫感染的疫苗，该模型模拟人宿主产生高滴度的抗α-Gal抗体。如预期的那样，感染了两种前鞭毛体的α-Gal-T基因敲除小鼠与野生型小鼠相比，利什曼原虫物种在肝脏中的寄生虫负荷显着降低，而在脾脏中的寄生虫水平则略有下降。Qβ-α-Gal纳米颗粒的疫苗接种可保护敲除小鼠抵抗利什曼原虫攻击，从而消除了qPCR所探测的肝脏和脾脏中寄生虫的感染和增殖。因此，α-Gal表位可以被认为是阻断人皮肤和内脏利什曼病的疫苗候选物。

更新日期：2017-09-13

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