Nasal immunization of mice with human papillomavirus type 16 (HPV-16) virus-like particles or with the HPV-16 L1 gene elicits specific cytotoxic T lymphocytes in vaginal draining lymph nodes
Nasal immunization of mice with human papillomavirus type 16 (HPV-16) virus-like particles or with the HPV-16 L1 gene elicits specific cytotoxic T lymphocytes in vaginal draining lymph nodes
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DOI：
10.1128/jvi.73.11.9063-9071.1999
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发表时间：
1999-11-01
影响因子：
5.4
通讯作者：
Coursaget, P
中科院分区：
文献类型：
--
作者：
Dupuy, C;Buzoni-Gatel, D;Coursaget, P
人乳头瘤病毒 16 型 (HPV-16) 感染生殖道，与宫颈癌的发生密切相关。 HPV-16在生殖器粘膜表面引发感染；因此，粘膜免疫反应可能有助于防御 HPV-16 感染。然而，关于在生殖道粘膜中诱导免疫反应的信息很少。在这项研究中，我们评估了鼻内注射乳头瘤病毒疫苗引发全身和阴道免疫反应的潜力。 L1蛋白自组装产生的HPV-16病毒样颗粒（VLP）和克隆到哺乳动物表达载体中的HPV-16 L1基因被用作疫苗。鼻内施用 VLP 诱导血清免疫球蛋白 G (IgG) 和阴道 IgA 分泌抗体。 DNA 免疫后发现血清 IgG 和阴道 IgA 反应非常弱。使用VLP和HPV-16 L1基因进行鼻内免疫可以激活脾脏和阴道淋巴细胞。激活的CD4(+) Th1样T细胞被证明可以合成γ干扰素，而激活的CD8(+) T细胞被证明具有细胞毒性。
Human papillomavirus type 16 (HPV-16) infects the genital tract and is closely associated with the development of cervical cancer. HPV-16 initiates infection at the genital mucosal surface; thus, mucosal immune responses are likely to contribute to defense against HPV-16 infection. However, little information is available regarding the induction of immune responses in the genital tract mucosa. In this study, we evaluated the potential of intranasally administered papillomavirus vaccines to elicit both systemic and vaginal immune responses. HPV-16 virus-like particles (VLPs) produced by self-assembly of L1 protein and the HPV-16 L1 gene cloned into a mammalian expression vector were used as vaccines. Intranasally administered VLPs induced serum immunoglobulin G (IgG) and vaginal IgA secretory antibodies. Very weak serum IgG and vaginal IgA responses were found after DNA immunization. Both splenic and vaginal lymphocytes could be activated by intranasal immunization with VLPs and the HPV-16 L1 gene. Activated CD4(+) Th1-like T cells were shown to synthesize gamma interferon, and activated CD8(+) T cells were demonstrated to be cytotoxic.