Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection.

Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection.
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DOI:
10.4049/jimmunol.0803740
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发表时间:
2009-12-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Czerkinsky C
Czerkinsky C
中科院分区:
其他
文献类型:
--
作者:
Cuburu N;Kweon MN;Hervouet C;Cha HR;Pang YY;Holmgren J;Stadler K;Schiller JT;Anjuère F;Czerkinsky C

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我们最近报道,舌下(s.l.)粘膜是诱导全身和粘膜免疫应答的有效部位。在这项研究中,s.l.通过使用非复制性Ag、OVA和霍乱毒素(CT)作为佐剂,在小鼠中检查免疫以诱导雌性生殖道中的远端Ab应答和CD 8+细胞毒性应答。舌下给药的OVA和CT诱导Ag特异性伊加和IgG抗体的血液和宫颈阴道分泌物。这些反应与大量的伊加抗体分泌细胞(ASCs)在生殖器粘膜。s.l.后生殖器ASC反应的幅度和同种型分布相似,鼻内或阴道免疫后观察到的,并且上级胃内免疫后观察到的。生殖器,但不是血液或脾脏,伊加ASC反应被抑制治疗与抗-CCL 28抗体,表明趋化因子CCL 28在伊加ASC祖细胞迁移到生殖道粘膜中起着重要作用。此外,S. L.用OVA免疫诱导生殖器粘膜中的OVA特异性效应CD 8+细胞溶解性T细胞,并且这些应答需要CT佐剂的共同施用。此外,S. L.在有或没有CT佐剂的情况下给予人乳头瘤病毒病毒样颗粒赋予了针对人乳头瘤病毒假病毒粒子的生殖器攻击的保护。总之,这些发现强调了s.l.的潜力。免疫接种是诱导生殖器免疫反应的有效疫苗接种战略,应能对性传播疾病疫苗的研制产生影响。
We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8+ cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8+ cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.
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发表时间: 2002-01-21
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影响因子: --
作者:
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发表时间: 1996-11-01
期刊: The Journal of experimental medicine
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DOI: 10.1006/viro.1996.0555
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