LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4+ and CD8+) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis

LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4+ and CD8+) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis
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DOI:
10.1186/1756-3305-7-61
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发表时间:
2014-02-07
影响因子:
3.2
通讯作者:
Reis, Alexandre Barbosa
Reis, Alexandre Barbosa
中科院分区:
医学2区
文献类型:
--
作者:
Aguiar-Soares, Rodrigo Dian de Oliveira;Roatt, Bruno Mendes;Reis, Alexandre Barbosa

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背景资料:开发犬内脏利什曼病(CVL)的保护性疫苗是中断婴儿利什曼原虫国内循环的另一种方法。鉴于白蛉唾液蛋白作为在利什曼原虫传播期间强制性共沉积的有效免疫原的重要性,在过去几十年中已经研究了将其包含在抗利什曼原虫疫苗中。在这种情况下,我们以前免疫狗与疫苗组成的L。巴西白蛉抗原加皂苷佐剂和白蛉唾液腺提取物(LBSapSal疫苗)。该疫苗引起抗唾液和抗利什曼原虫IgG同种型的增加,特异性循环CD 8(+)T细胞的更高计数,以及高NO production.Methods:我们研究了LBSapSal疫苗接种后皮内攻击1 × 10(7)晚对数期L.在长须陆蚊的沙蝇唾液存在下的婴儿前鞭毛体。结果:LBSapSal疫苗具有广泛的抗原多样性,并具有持续的体液和细胞免疫应答,表明对CVL的抵抗是由高水平的总IgG及其亚型触发的(IgG 1和IgG 2);循环CD 5(+)、CD 4(+)和CD 8(+)T淋巴细胞的扩增,并且是利什曼原虫特异性的;以及脾寄生虫负荷的减少。这些结果鼓励进一步研究针对利什曼原虫抗原与载体唾液中存在的蛋白质组合的疫苗策略。
Background: The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8(+) T cells, and high NO production.Methods: We investigated the immunogenicity and protective effect of LBSapSal vaccination after intradermal challenge with 1 x 10(7) late-log-phase L. infantum promastigotes in the presence of sand fly saliva of Lutzomyia longipalpis. The dogs were followed for up to 885 days after challenge.Results: The LBSapSal vaccine presents extensive antigenic diversity with persistent humoral and cellular immune responses, indicating resistance against CVL is triggered by high levels of total IgG and its subtypes (IgG1 and IgG2); expansion of circulating CD5(+), CD4(+), and CD8(+) T lymphocytes and is Leishmania-specific; and reduction of splenic parasite load.Conclusions: These results encourage further study of vaccine strategies addressing Leishmania antigens in combination with proteins present in the saliva of the vector.