The Mucosal Adjuvant Effect of α-Galactosylceramide for Induction of Protective Immunity to Sexually Transmitted Viral Infection
The Mucosal Adjuvant Effect of α-Galactosylceramide for Induction of Protective Immunity to Sexually Transmitted Viral Infection
复制标题
DOI：
10.4049/jimmunol.0900136
复制
发表时间：
2009-05-15
影响因子：
4.4
通讯作者：
Harandi, Ali M.
中科院分区：
文献类型：
--
作者：
Lindqvist, Madelene;Persson, Josefine;Harandi, Ali M.
发展粘膜佐剂在女性生殖道产生免疫力可能对发展对抗性传播感染的疫苗具有重要意义。α-半乳糖神经酰胺（α-GalCer）由APC上的CD 1d分子呈递给不变V α 14（+）NKT（iNKT）细胞，其在活化后迅速产生大量免疫调节细胞因子，导致多种先天性和适应性免疫细胞的活化。在这里，我们评估了α-GalCer是否可以作为粘膜佐剂诱导对生殖器疱疹的保护性免疫。我们发现，用HSV-2糖蛋白D（gD）与α-GalCer组合的鼻内免疫激发了强烈的全身性gD特异性IgG Ab应答以及在脾、纵隔淋巴结和生殖器淋巴结中具有混合的Th 1/Th 2细胞因子谱的淋巴增殖应答。重要的是，这样的免疫方案赋予了针对所有其他致命的阴道HSV-2攻击的完全保护。我们还可以表明，阴道内免疫gD加α-GalCer产生有效的gD特异性淋巴增殖和IFN-γ反应在生殖器淋巴结和脾脏。此外，阴道免疫的小鼠产生了强烈的全身和粘膜IgG Ab应答和对阴道HSV-2攻击的保护。发现alpha-GalCer的粘膜佐剂作用是通过CD 1d分子介导的，并且似乎不依赖于衔接分子MyD 88的使用。据我们所知，这是关于α-GalCer诱导针对性传播病原体的保护性免疫的粘膜佐剂作用的第一份报告。免疫学杂志，2009，182：6435-6443.
Development of mucosal adjuvants to generate immunity in the female genital tract may have important implications for the development of vaccines to counter sexually transmitted infections. alpha-Galactosylceramide (alpha-GalCer) is presented by CD1d molecule on APCs to invariant V alpha 14(+) NKT (iNKT) cells, which upon activation rapidly produce large amounts of immunomodulatory cytokines, leading to activation of a variety of innate and adaptive immune cells. Here, we assessed whether alpha-GalCer could act as a mucosal adjuvant for induction of protective immunity against genital herpes. We found that intranasal immunization with HSV-2 glycoprotein D (gD) in combination with alpha-GalCer elicits strong systemic gD-specific IgG Ab response as well as lymphoproliferative response with a mixed Th1/Th2 cytokine profile in the spleen, mediastinal lymph nodes, and genital lymph nodes. Importantly, such an immunization scheme conferred complete protection against ail otherwise lethal vaginal HSV-2 challenge. We could also show that intravaginal immunization with gD plus alpha-GalCer generates potent gD-specific lymphoproliferative and IFN-gamma responses in the genital lymph nodes and spleen. Furthermore, the vaginally immunized mice developed a strong systemic and mucosal IgG Ab response and protection against vaginal HSV-2 challenge. The mucosal adjuvant effect of alpha-GalCer was found to be mediated via CD1d molecule and appeared to be independent of the usage of the adaptor molecule MyD88. To our knowledge, this is the first report on the mucosal adjuvant effect of alpha-GalCer for induction of protective immunity against a sexually transmitted pathogen. The Journal of Immunology, 2009, 182: 6435-6443.