2002 年度実績報告書

粘膜ワクチンへの基礎研究:HIV特異的分泌型IgA誘導システムの開発

研究課題

研究課題/領域番号	14021068
研究機関	東京大学
研究代表者	清野宏東京大学, 医科学研究所, 教授 (10271032)
キーワード	粘膜免疫 / 粘膜ワクチン / 粘膜アジュバント / HIVワクチン / 分泌型IgA
研究概要	粘膜免疫システムを駆使してHIVに対する第一線のバリアを構築するには、経口・経ワクチンが有効であり、その鍵を握っているのが安全で免疫増強作用の強い粘膜アジュバントと粘膜ワクチンデリバリー法の開発である。本研究計画では、B. choshinesis発現ベクターシステムを使った新規のmCT-A/LT-Bキメラ分子を使用したHIVワクチン用粘膜アジュバント開発に関連する基礎研究を展開した。さらに、経鼻ワクチン開発へ向けての基礎情報収集目的で、その中枢的役割を果たすNALTと呼ばれる粘膜関連リンパ組織の組織形成プログラムについても検討を行った。また、NALTを介した粘膜免疫システムの活性化に有効な新型粘膜ワクチン抗原デリバリー法であるFLのHIV特異的免疫応答の有効性についても詳細な検討を進めた。例えば、FLにHIVgp160を封入(FL-gp160)し正常マウスに経鼻免疫すると、効果的にHIV侵入門戸である生殖器粘膜系に抗原特異的分泌型IgAとIgG抗体を誘導出来る事を確認した。さらに、血清中にもHIV抗原特異的IgG抗体が誘導される。つまり、FLワクチン抗原封入体により二段構えのHIV特異的免疫応答が粘膜系と全身系両方に惹起させる事が出来る事を見出した。

研究成果
(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Fukuyama, S., Kiyono, K., et al.: "NALT organogenesisn is independent of the IL-7R, LT α1β2/LTβR and NIK signaling pathways but does require the Id2 gene and CD3^-CD4^+CD45^+ cells"Immunity. 17. 31-40 (2002)
[文献書誌] Sakaue, G., Kiyono, H., et al.: "HIV mucosal vaccine : nasal immunization with gp160 enapsulated HVJ-liposome induces antigen-specific CTL and neutralizing antibody responses"J. Immunol.. 170. 495-502 (2002)
[文献書誌] Kweon, M-N., Kiyono, K., et al.: "A non-toxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE Ab"J. Infect. Dis.. 186. 1261-1269 (2002)
[文献書誌] Watanabe, I., Kiyono, H., et al.: "Characterization of protective immune responses induced by nasal influenza vaccine ccontaining mutant cholera toxin as a safe adjuvant (CT112K)"Vaccine. 20. 3443-3455 (2002)
[文献書誌] Kawahara, M., Kiyono, H., et al.: "Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen"Vaccine. 21. 158-166 (2002)
[文献書誌] Hamada, H., Kiyono, H., et al.: "Identification of multipe isolated lymphoid follicled on the antimesenteric wall of the mouse small intestine"J. Immunol.. 168. 57-64 (2002)
[文献書誌] Kweon, M-N., Kiyono, H., et al.: "Development of antigen-induced enterocolitis in SCID mice reconstituted with spleen-derived memory type CD4^+ CD45RB^+ T cells"Gut. 50. 299-306 (2002)
[文献書誌] Takahashi, I., Kiyono, H., et al.: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10 deficient mice"Clin. Immunol.. 102. 237-248 (2002)
[文献書誌] Kunisawa, J., Kiyono, H., et al.: "Lack of antigen-specific immune responses in anti-IL-7α antibody-treated Peyer's patch-null mice following intestinal immunization with microencapsulated antigen"Eur. J. Immunol.. 32. 2347-2355 (2002)
[文献書誌] Ohta, N., Kiyono, H., et al.: "IL-15 induced CD8αβ^+ NK1.1^+T cells in the development of small itestinal inflammation in T3b-IL-15 Tg mice"J. Immunol.. 169. 460-468 (2002)
[文献書誌] Suenobu, N., Kiyono, H., et al.: "Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs : a possibility for the control of Candida-related atopic dermatitis"Vaccine. 20. 2972-2980 (2002)
[文献書誌] Ueta, M., Kiyono, H., et al.: "Immunosuppressive properties of human aminiotic membarane for mixed lymphocyte reaction"Clin. Exp. Immunol.. 129. 464-470 (2002)
[文献書誌] Kweon, M-N., Kiyono, H.: "CD40L in auto immunity and mucosally induced tolerance"J. Clin. Invest.. 109. 171-173 (2002)
[文献書誌] Yanagita, M., Kiyono, H.et al.: "IL-15 up-regulates iNOS expression and NO production by gingval epithelial cells"Biochem. Biophysical. Res. Commun. 297. 329-334 (2002)
[文献書誌] Kinoshita, N., Kiyono, H., et al.: "Autocrine IL-15 mediates intestinal epithelial cell death via the activation of neighboring intraepithelial NK cells"J. Immunol.. 169. 6187-6192 (2002)
[文献書誌] Enose, Y., Kiyono, H., et al.: "Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV"Virology. 298. 306-316 (2002)
[文献書誌] Okuda, Y., Kiyono, H., et al.: "Development of colitis in STAT6-deficient TCRα^<-/-> mice : A potential of STAT6-independent IL-4 signaling for the generation of Th2-biased pathologic CD4^+ββT cells"Am. J. Pathol.. 162. 263-271 (2003)
[文献書誌] Boyaka, P.N., Kiyono, H., et al.: "Chimeras of labile toxin one and cholera toxin retain mucosal adjuvanticity and direct Th cell subsets via their B subunit"J. Immunol.. 170. 454-462 (2003)
[文献書誌] Hagiwara, Y., Kiyono, H., et al.: "Protective mucosal immunity in aging is associated with functional CD4^+T cells in nasopharyngeal-associated lymphoreticular tissue"J. Immunol.. 15. 1754-1762 (2003)

2002 年度 実績報告書

粘膜ワクチンへの基礎研究:HIV特異的分泌型IgA誘導システムの開発

研究代表者

清野 宏 東京大学, 医科学研究所, 教授 (10271032)

研究成果

[文献書誌] Fukuyama, S., Kiyono, K., et al.: "NALT organogenesisn is independent of the IL-7R, LT α1β2/LTβR and NIK signaling pathways but does require the Id2 gene and CD3^-CD4^+CD45^+ cells"Immunity. 17. 31-40 (2002)

[文献書誌] Sakaue, G., Kiyono, H., et al.: "HIV mucosal vaccine : nasal immunization with gp160 enapsulated HVJ-liposome induces antigen-specific CTL and neutralizing antibody responses"J. Immunol.. 170. 495-502 (2002)

[文献書誌] Kweon, M-N., Kiyono, K., et al.: "A non-toxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE Ab"J. Infect. Dis.. 186. 1261-1269 (2002)

[文献書誌] Watanabe, I., Kiyono, H., et al.: "Characterization of protective immune responses induced by nasal influenza vaccine ccontaining mutant cholera toxin as a safe adjuvant (CT112K)"Vaccine. 20. 3443-3455 (2002)

[文献書誌] Kawahara, M., Kiyono, H., et al.: "Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen"Vaccine. 21. 158-166 (2002)

[文献書誌] Hamada, H., Kiyono, H., et al.: "Identification of multipe isolated lymphoid follicled on the antimesenteric wall of the mouse small intestine"J. Immunol.. 168. 57-64 (2002)

[文献書誌] Kweon, M-N., Kiyono, H., et al.: "Development of antigen-induced enterocolitis in SCID mice reconstituted with spleen-derived memory type CD4^+ CD45RB^+ T cells"Gut. 50. 299-306 (2002)

[文献書誌] Takahashi, I., Kiyono, H., et al.: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10 deficient mice"Clin. Immunol.. 102. 237-248 (2002)

[文献書誌] Kunisawa, J., Kiyono, H., et al.: "Lack of antigen-specific immune responses in anti-IL-7α antibody-treated Peyer's patch-null mice following intestinal immunization with microencapsulated antigen"Eur. J. Immunol.. 32. 2347-2355 (2002)

[文献書誌] Ohta, N., Kiyono, H., et al.: "IL-15 induced CD8αβ^+ NK1.1^+T cells in the development of small itestinal inflammation in T3b-IL-15 Tg mice"J. Immunol.. 169. 460-468 (2002)

[文献書誌] Suenobu, N., Kiyono, H., et al.: "Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs : a possibility for the control of Candida-related atopic dermatitis"Vaccine. 20. 2972-2980 (2002)

[文献書誌] Ueta, M., Kiyono, H., et al.: "Immunosuppressive properties of human aminiotic membarane for mixed lymphocyte reaction"Clin. Exp. Immunol.. 129. 464-470 (2002)

[文献書誌] Kweon, M-N., Kiyono, H.: "CD40L in auto immunity and mucosally induced tolerance"J. Clin. Invest.. 109. 171-173 (2002)

[文献書誌] Yanagita, M., Kiyono, H.et al.: "IL-15 up-regulates iNOS expression and NO production by gingval epithelial cells"Biochem. Biophysical. Res. Commun. 297. 329-334 (2002)

[文献書誌] Kinoshita, N., Kiyono, H., et al.: "Autocrine IL-15 mediates intestinal epithelial cell death via the activation of neighboring intraepithelial NK cells"J. Immunol.. 169. 6187-6192 (2002)

[文献書誌] Enose, Y., Kiyono, H., et al.: "Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV"Virology. 298. 306-316 (2002)

[文献書誌] Okuda, Y., Kiyono, H., et al.: "Development of colitis in STAT6-deficient TCRα^<-/-> mice : A potential of STAT6-independent IL-4 signaling for the generation of Th2-biased pathologic CD4^+ββT cells"Am. J. Pathol.. 162. 263-271 (2003)

[文献書誌] Boyaka, P.N., Kiyono, H., et al.: "Chimeras of labile toxin one and cholera toxin retain mucosal adjuvanticity and direct Th cell subsets via their B subunit"J. Immunol.. 170. 454-462 (2003)

[文献書誌] Hagiwara, Y., Kiyono, H., et al.: "Protective mucosal immunity in aging is associated with functional CD4^+T cells in nasopharyngeal-associated lymphoreticular tissue"J. Immunol.. 15. 1754-1762 (2003)

2002 年度実績報告書

清野宏東京大学, 医科学研究所, 教授 (10271032)