A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge.
A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge.
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DOI：
10.1038/mi.2008.81
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发表时间：
2009-03
影响因子：
8
通讯作者：
BenMohamed L
中科院分区：
文献类型：
--
作者：
Zhang X;Chentoufi AA;Dasgupta G;Nesburn AB;Wu M;Zhu X;Carpenter D;Wechsler SL;You S;BenMohamed L
下一代无针粘膜疫苗正在根据控制表位被生殖器粘膜免疫系统识别并刺激生殖器粘膜免疫系统的方式的规则进行合理设计。我们假设，用 Toll 样受体 2 (TLR-2) 激动剂延伸的合成肽表位（阴道粘膜的树突状细胞和上皮细胞大量表达）将导致诱导针对生殖器疱疹的保护性免疫。为了检验这一假设，我们使用由棕榈酸部分（一种 TLR-2 激动剂）延伸的单纯疱疹病毒 2 型 (HSV-2) CD8+ T 细胞肽表位，对野生型 B6、TLR-2 (TLR2−/−) 或骨髓分化因子 88 缺陷型 (MyD88−/−) 小鼠进行阴道内 (IVAG) 免疫。脂肽的 IVAG 递送在生殖道引流淋巴结局部和脾脏中产生 HSV-2 特异性记忆 CD8+ 细胞毒性 T 细胞。此外，与脂肽免疫的野生型 B6 小鼠相比，脂肽免疫的 TLR2−/− 和 MyD88−/− 小鼠的 HSV 特异性 CD8+ T 细胞反应明显减少，死亡更早，疾病进展更快，阴道 HSV-2 滴度更高。使用自我辅助脂尾肽进行 IVAG 免疫似乎是一种新型的粘膜疫苗方法，具有有吸引力的实用和免疫学特征。
The next generation of needle-free mucosal vaccines is being rationally designed according to rules that govern the way in which the epitopes are recognized by and stimulate the genital mucosal immune system. We hypothesized that synthetic peptide epitopes extended with an agonist of Toll-like receptor 2 (TLR-2), that are abundantly expressed by dendritic and epithelial cells of the vaginal mucosa, would lead to induction of protective immunity against genital herpes. To test this hypothesis, we intravaginally (IVAG) immunized wild-type B6, TLR-2 (TLR2−/−) or myeloid differentiation factor 88 deficient (MyD88−/−) mice with a herpes simplex virus type 2 (HSV-2) CD8+ T-cell peptide epitope extended by a palmitic acid moiety (a TLR-2 agonist). IVAG delivery of the lipopeptide generated HSV-2-specific memory CD8+ cytotoxic T cells both locally in the genital tract draining lymph nodes and systemically in the spleen. Moreover, lipopeptide-immunized TLR2−/− and MyD88−/− mice developed significantly less HSV-specific CD8+ T-cell response, earlier death, faster disease progression, and higher vaginal HSV-2 titers compared to lipopeptide-immunized wild-type B6 mice. IVAG immunization with self-adjuvanting lipid-tailed peptides appears to be a novel mucosal vaccine approach, which has attractive practical and immunological features.