Department of Molecular Microbiology and Immunology, Saint Louis University Medical Center, St. Louis, Missouri 63104, USA.
Infect Immun. 2010 Mar;78(3):1333-8. doi: 10.1128/IAI.00278-09. Epub 2010 Jan 4.
Trypanosoma cruzi is an intracellular protozoan parasite capable of infecting through mucosal surfaces. Our laboratory has previously elucidated the anatomical routes of infection after both conjunctival and gastric challenge in mice. We have shown that chronically infected mice develop strong immune responses capable of protecting against subsequent rechallenge with virulent parasites through gastric, conjunctival, and systemic routes of infection. We have also shown that intranasal immunizations with the unique T. cruzi trans-sialidase (TS) antigen protect against gastric and systemic T. cruzi challenge. In the current work we have investigated the ability of purified TS adjuvanted with CpG-containing oligonucleotides to induce immunity against conjunctival T. cruzi challenge. We confirm that intranasal vaccinations with TS plus CpG induce TS-specific T-cell and secretory IgA responses. TS-specific secretory IgA was detectable in the tears of vaccinated mice, the initial body fluid that contacts the parasite during infectious conjunctival exposures. We further show that intranasal vaccinations with TS plus CpG protect against conjunctival T. cruzi challenge, limiting local parasite replication at the site of mucosal invasion and systemic parasite dissemination. We also provide the first direct evidence that mucosal antibodies induced by intranasal TS vaccination can inhibit parasite invasion.
克氏锥虫是一种能够通过黏膜表面感染的细胞内原生动物寄生虫。我们的实验室之前已经阐明了在小鼠的结膜和胃刺激后感染的解剖途径。我们已经表明，慢性感染的小鼠会产生强烈的免疫反应，能够通过胃、结膜和全身感染途径保护免受随后的强毒寄生虫再攻击。我们还表明，用独特的克氏锥虫转涎酸酶（TS）抗原经鼻内免疫可预防胃和全身克氏锥虫感染。在目前的工作中，我们研究了用含有 CpG 寡核苷酸佐剂的纯化 TS 诱导针对结膜克氏锥虫感染的免疫能力。我们证实，用 TS 加 CpG 进行鼻内接种可诱导 TS 特异性 T 细胞和分泌型 IgA 反应。在接种疫苗的小鼠的泪液中可检测到 TS 特异性分泌型 IgA，这是在传染性结膜暴露期间接触寄生虫的初始体液。我们进一步表明，用 TS 加 CpG 进行鼻内接种可预防结膜克氏锥虫感染，限制了黏膜入侵部位的局部寄生虫复制和全身寄生虫传播。我们还提供了第一个直接证据，证明经鼻内 TS 接种诱导的黏膜抗体可以抑制寄生虫入侵。
