de Jesus Pereira Nathália Cristina, Régis Wiliam César Bento, Costa Lourena Emanuele, de Oliveira Jamil Silvano, da Silva Alanna Gomes, Martins Vivian Tamietti, Duarte Mariana Costa, de Souza José Roberto Rodrigues, Lage Paula Sousa, Schneider Mônica Santos, Melo Maria Norma, Soto Manuel, Soares Sandra Aguiar, Tavares Carlos Alberto Pereira, Chávez-Fumagalli Miguel Angel, Coelho Eduardo Antonio Ferraz
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
Instituto de Ciências Biológicas e da Saúde, Pontifícia Universidade Católica de Minas Gerais, 30535-901 Belo Horizonte, Minas Gerais, Brazil; Minasfungi do Brasil Ltda, Belo Horizonte, Minas Gerais, Brazil.
Exp Parasitol. 2015 Jun;153:180-90. doi: 10.1016/j.exppara.2015.03.027. Epub 2015 Apr 3.
The development of effective prophylactic strategies to prevent leishmaniasis has become a high priority. No less important than the choice of an antigen, the association of an appropriate adjuvant is necessary to achieve a successful vaccination, as the majority of the tested antigens contain limited immunogenic properties, and need to be supplemented with immune response adjuvants in order to boost their immunogenicity. However, few effective adjuvants that can be used against leishmaniasis exist on the market today; therefore, it is possible to speculate that the research aiming to identify new adjuvants could be considered relevant. Recently, Agaricus blazei extracts have proved to be useful in enhancing the immune response to DNA vaccines against some diseases. This was based on the Th1 adjuvant activity of the polysaccharide-rich fractions from this mushroom. In this context, the present study evaluated purified fractions derived from Agaricus blazei as Th1 adjuvants through in vitro assays of their immune stimulation of spleen cells derived from naive BALB/c mice. Two of the tested six fractions (namely F2 and F4) were characterized as polysaccharide-rich fractions, and were able to induce high levels of IFN-γ, and low levels of IL-4 and IL-10 in the spleen cells. The efficacy of adjuvant action against L. infantum was evaluated in BALB/c mice, with these fractions being administered together with a recombinant antigen, LiHyp1, which was previously evaluated as a vaccine candidate, associated with saponin, against visceral leishmaniasis (VL). The associations between LiHyp1/F2 and LiHyp1/F4 were able to induce an in vivo Th1 response, which was primed by high levels of IFN-γ, IL-12, and GM-CSF, by low levels of IL-4 and IL-10; as well as by a predominance of IgG2a antibodies in the vaccinated animals. After infection, the immune profile was maintained, and the vaccines proved to be effective against L. infantum. The immune stimulatory effects in the BALB/c mice proved to be similar when comparing the F2 and F4 fractions with a known Th1 adjuvant (saponin), though animals vaccinated with saponin did present a slight to moderate inflammatory edema on their hind footpads. In conclusion, the F2 and F4 fractions appear to induce a Th1-type immune response and, in this context, they could be evaluated in association with other protective antigens against Leishmania, as well as in other disease models.
开发有效的预防利什曼病的策略已成为当务之急。与选择抗原同样重要的是，为了成功接种疫苗，必须搭配合适的佐剂，因为大多数测试抗原的免疫原性有限，需要辅以免疫反应佐剂以增强其免疫原性。然而，目前市场上可用于对抗利什曼病的有效佐剂很少；因此，可以推测旨在鉴定新佐剂的研究可能具有相关性。最近，巴西蘑菇提取物已被证明有助于增强针对某些疾病的DNA疫苗的免疫反应。这是基于该蘑菇富含多糖的组分的Th1佐剂活性。在此背景下，本研究通过体外检测巴西蘑菇纯化组分对未接触过抗原的BALB/c小鼠脾细胞的免疫刺激作用，评估其作为Th1佐剂的效果。测试的六个组分中有两个（即F2和F4）被鉴定为富含多糖的组分，能够在脾细胞中诱导高水平的IFN-γ以及低水平的IL-4和IL-10。在BALB/c小鼠中评估了这些组分作为针对婴儿利什曼原虫的佐剂作用的效果，这些组分与重组抗原LiHyp1一起给药，LiHyp1先前被评估为与皂苷联合用于抗内脏利什曼病（VL）的候选疫苗。LiHyp1/F2和LiHyp1/F4的组合能够诱导体内Th1反应，其特征为高水平的IFN-γ、IL-12和GM-CSF，低水平的IL-4和IL-10；以及接种疫苗的动物中IgG2a抗体占优势。感染后，免疫特征得以维持，并且这些疫苗被证明对婴儿利什曼原虫有效。将F2和F4组分与已知的Th1佐剂（皂苷）进行比较时，在BALB/c小鼠中的免疫刺激作用被证明是相似的，尽管接种皂苷的动物后脚垫出现了轻度至中度的炎性水肿。总之，F2和F4组分似乎能诱导Th1型免疫反应，在此背景下，它们可与其他抗利什曼原虫的保护性抗原联合进行评估，也可在其他疾病模型中进行评估。
