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ORALLY ADMINISTERED HPV 16 VACCINE STIMULATING GUT-ASSOCIATED LYMPHOID TISSUES

口服 HPV 16 疫苗刺激肠道相关淋巴组织

基本信息

批准号：
13671701
负责人：
SASAGAWA Toshiyuki
金额：
$ 0.64万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671701/
关键词：
Human pgpillomavirus Prophylactic vaccine Virus-like particles Cervical cancer Oral vaccine Mouse model system Cholera Toxin 診断法分子疫学

项目摘要

Human papillomavirus type16 (HPV16) is the most important risk factor for cervical cancer. Thus, effective prophylactic vaccine against HPV 16 is expected for prevention of cervical cancer development, which is the secondary common cancer of women worldwide.Recent study showed that nasal administration of HPV16 virus-like particles (VLP) is able to elicit mucosal antibody neutralizing HPV 16. In the present study, we tested an efficacy of orally administered HPV16 vaccine using yeast synthesizing HPV 16 VLP (HPV 16 VLP-yeast). Preliminary experiments showed that freeze dried yeast was good candidate for delivering antigen to the gut and stimulating the gut-associated lymphoid tissues (GALT), since it was not digested in the stomach but digested in the intestine.Positive control mice were nasally administered with purified HPV16 VLP (Nasal-Ad), and the others were orally administered with freeze dried yeast (Oral-Ad). Two mice were orally administered with control yeast, two mice with HPV6 VLP-yeast, 6 mice with HPv16 VLP-yeast, and 12 mice with HPV16 VLP-yeast and Cholera toxin (CT). HPV-specific antibody responses were tested with HPV6- and 16-VLP-ELISA. Two Nasal-Ad mice, 3 of 6 Oral-Ad mice with HPV16 VLP-yeast, and 4 of 12 Oral-Ad mice with HPV 16 VLP-yeast + CT elicited HPV 16-specific IgA and IgG serum antibody (Ab), whereas mice administered with control yeast or with HPV6-VLP-yeast had no such responses.The liters of the serum Ab were as high as those in the mice nasally administered with HPV16 VLP, and no difference in serum Ab titers was observed by administrating CT or not. Weak but HPV 16-specifc IgA responses were detected in vaginal secretions of 2 of 12 Oral-Ad mice with CT. Now we are optimizing the condition able to induce stronger mucosal IgA response.

人乳头瘤病毒16型（HPV 16）是宫颈癌最重要的危险因素。因此，有效的HPV 16预防性疫苗有望预防宫颈癌（全球女性常见的第二种癌症）的发生。最近的研究表明，经鼻给予HPV 16病毒样颗粒（VLP）能够激发中和HPV 16的粘膜抗体。在本研究中，我们使用合成HPV 16 VLP的酵母（HPV 16 VLP-酵母）检测了口服HPV 16疫苗的有效性。初步实验表明，冻干酵母在胃中不被消化，而在肠中被消化，是将抗原递送到肠道并刺激肠道相关淋巴组织（GALT）的良好候选物。给两只小鼠口服对照酵母，给两只小鼠口服HPV 6 VLP-酵母，给6只小鼠口服HPV 16 VLP-酵母，给12只小鼠口服HPV 16 VLP-酵母和霍乱毒素（CT）。用HPV 6-和16-VLP-ELISA检测HPV特异性抗体应答。2只Nasal-Ad小鼠、6只经口给予HPV 16 VLP-酵母的Oral-Ad小鼠中的3只和12只经口给予HPV 16 VLP-酵母+ CT的Oral-Ad小鼠中的4只可诱发HPV 16特异性伊加和IgG血清抗体（Ab），而给予对照酵母或HPV 6-VLP-酵母的小鼠则无此反应。而血清Ab滴度在CT给药前后无明显差异。12只Oral-Ad小鼠中有2只的阴道分泌物中检测到弱但HPV 16特异性伊加反应。现在我们正在优化能够诱导更强的粘膜伊加反应的条件。