1997 年度実績報告書

抗原特異的細胞障害性T細胞の活性化による微生物に対する感染防御の検討

研究課題

研究課題/領域番号	09670293
研究種目	基盤研究(C)
研究機関	横浜市立大学
研究代表者	奥田研爾横浜市立大学, 医学部, 教授 (40124862)
研究分担者	浜島健治横浜市立大学, 医学部, 助手 (00114611) 青木一郎横浜市立大学, 医学部, 助教授 (00184028)
キーワード	DNAワクチン / HIV-1 / Th1細胞 / IL-I2 / gp160 / 粘膜免疫
研究概要	今回の補助金により、細胞内寄生性微生物(特にHIV)のDNAワクチンの効果について、検討を行った。今までに作製されているDNAワクチンは他のウイルス等、例えば我々の実験ではインフルエンザウイルスについてはM抗原を発現するDNAワクチンを作製する事により、感染防御効果が認められた。しかし、HIV-1については今の所チンパンジー、アカゲザル等を使用した系では、DNAワクチンでは抗体の産生があまり強くないため、我々のデータを含めて目覚しい防御効果が低いように思われる。今回のマウスを使用した検討では、DNAワクチンはCTLを主とするTh1細胞の活性化を起こし、その活性化をIL-I2、IFN-γ、IL-I2等の発現プラスミドと共に免疫することにより強く発現されることが判明した。しかし、MuLV/HIV-1キメラウイルスを使用した実験では1)GP160、Tat、Nef等の蛋白を3度免疫したグループは、これらの抗原に対する抗体価は非常に高かったが、キメラウイルスの注入により感染抵抗が獲得できなかった。2)次に、env、tat、nefのDNAワクチンを免疫したグループは、同様のキメラウイルスの注入に対して完全に感染抵抗性が獲得されており、抗体価はあまり高くないが、細胞障害性T細胞活性(CTL)が高かった。3)一方、これらDNAワクチンとIL-2の発現系プラスミドを同時に免疫したグループは、CTL活性が極めて高いにもかかわらず抗体価はほとんど検出されなかった。しかしながらこの群はキメラウイルスのchallengeに部分的にしか感染防御能は獲得し得なかった。以上の結果、我々は現在のHIV-1ワクチンの有効性を得るためにはHIV-1に対する中和抗体と、CTLを主とするTh1タイプの反応性の両方に免疫原性のあるワクチンは最も有効であると思っている。

研究成果

(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Tsuji T., et al.: "Enhahcement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12." J.Immunol. 158. 4008-4014 (1997)
[文献書誌] Tsuji T., et al.: "Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen." Eur.J.Immunol.27. 782-787 (1997)
[文献書誌] Tsuji T., et al.: "HIV-1 specific cell-mediated immunity is enhanced by co-inoculation of TCA3 expression plasmid with DNA vaccine" Immunol.90. 1-6 (1997)
[文献書誌] Okuda K., et al.: "DNA vaccination followed bu macromolecular multicomponent peptide vaccination against HIV-1 induces strong antigen-specific immunity." Vaccine. 15. 1049-1056 (1997)
[文献書誌] Sasaki S., et al.: "Human immunodeficiency virus type 1 specific immune responses induced by DNA vaccination are greatly enhanced by mannan-coated diC14-amidine." Eur.J Immunol.27. 3121-3129 (1997)
[文献書誌] Hamajima K., et al.: "Strong augment effect of IL-12 expression plasmid on the induction of HIV specific cytotoxic Iymphocyte(CTL)activity by peptide vaccine candidate." Clin.Immunol.Immunopath.23. 179-184 (1997)
[文献書誌] Hinkula J., et al.: "Prominant viral epitope recognition by DNA-based immunization with regulatory HIV-1 genes." J.Virol.71. 5528-5539 (1997)
[文献書誌] Ishii N., et al.: "Cationic liposomes are a strong adjuvant of DNA vaccine for a human immunodificiency virus type-1(HIV-1)" AIDS Res.Hum.Retrov.13. 1421-1428 (1997)
[文献書誌] Sasaki S., et al.: "Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against Human Immunodeficiency Virus Type 1." Infect.Immun.65. 3520-3528 (1997)
[文献書誌] Asakura Y., et al.: "Induction of HIV-1 specific mucosal immune responses by DNA vaccination." Scand.J.Immunol.46. 326-330 (1997)
[文献書誌] Toda S., et al.: "HIV-1 specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomea and inhibited by anti-interferon(IFN)-γ antibody." Immunology. 92. 111-117 (1997)
[文献書誌] Mor G., et al.: "Do DNA vaccines induce autoimmune disease?" Hum.Gene.Ther.8. 293-300 (1997)
[文献書誌] Tanabe S., et al.: "Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes." J.Immunol.159. 905-911 (1997)
[文献書誌] Mohri H., et al.: "Synthetic peptide from the V3 loop consensus motif with A potent anti-HIV activity inhibits ristocetin-mediated VWF-GPlb interaction" Peptide. 18. 1289-1293 (1997)
[文献書誌] Ishii N., et al.: "Genetic control of immune responses to HIV-1 env DNA vaccine." Microbiol.Immunol.41. 421-425 (1997)
[文献書誌] Okada E., et al.: "Intranasal immunization of a DNA vaccine with interleukin 12 and granulocyte macrophage colony stimulating factor(GM-CSF)expressing plasmids in liposomes induce strong mucosal and cell-mediated immune responses" J.Immunol.159. 3638-3647 (1997)
[文献書誌] Sasaki S., et al.: "A comparison of intranasal and intramuscular DNA vaccination against human immunodeficiency virus type 1 with monophosphoryl lipid A adjuvant." Infect.Immun.66. 823-826 (1998)
[文献書誌] Sasaki S., et al.: "Adjuvant effect of ubenimex on the responses induced by DNA vaccine for human immunodeficiency virus type-1" Clin.Exp.Immunol.111. 30-36 (1998)
[文献書誌] Xin K.-Q., et al.: "Intranasal administration of HIV-1 DNA vaccine with IL-2 expression plasmid enhances cell-mediated" Immunology. (in press). (1998)
[文献書誌] Sasaki S., et al: "Induction systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 adjuvant via intramuscular and intranasal routes." J.Virol.(in press). (1998)
[文献書誌] OKuda K., et al.: "Methods in molecular biology(ed.D.B.Iowire)." Humana press,Totowa,NJ.(in press), (1997)
[文献書誌] Sasaki S.& Okuda K.: "Methods in molecular biology(ed.D.B.Iowire)." Humana press,Totowa,NJ.(in press), (1997)

1997 年度 実績報告書

抗原特異的細胞障害性T細胞の活性化による微生物に対する感染防御の検討

研究代表者

奥田 研爾 横浜市立大学, 医学部, 教授 (40124862)

研究成果

[文献書誌] Tsuji T., et al.: "Enhahcement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12." J.Immunol. 158. 4008-4014 (1997)

[文献書誌] Tsuji T., et al.: "Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen." Eur.J.Immunol.27. 782-787 (1997)

[文献書誌] Tsuji T., et al.: "HIV-1 specific cell-mediated immunity is enhanced by co-inoculation of TCA3 expression plasmid with DNA vaccine" Immunol.90. 1-6 (1997)

[文献書誌] Okuda K., et al.: "DNA vaccination followed bu macromolecular multicomponent peptide vaccination against HIV-1 induces strong antigen-specific immunity." Vaccine. 15. 1049-1056 (1997)

[文献書誌] Sasaki S., et al.: "Human immunodeficiency virus type 1 specific immune responses induced by DNA vaccination are greatly enhanced by mannan-coated diC14-amidine." Eur.J Immunol.27. 3121-3129 (1997)

[文献書誌] Hamajima K., et al.: "Strong augment effect of IL-12 expression plasmid on the induction of HIV specific cytotoxic Iymphocyte(CTL)activity by peptide vaccine candidate." Clin.Immunol.Immunopath.23. 179-184 (1997)

[文献書誌] Hinkula J., et al.: "Prominant viral epitope recognition by DNA-based immunization with regulatory HIV-1 genes." J.Virol.71. 5528-5539 (1997)

[文献書誌] Ishii N., et al.: "Cationic liposomes are a strong adjuvant of DNA vaccine for a human immunodificiency virus type-1(HIV-1)" AIDS Res.Hum.Retrov.13. 1421-1428 (1997)

[文献書誌] Sasaki S., et al.: "Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against Human Immunodeficiency Virus Type 1." Infect.Immun.65. 3520-3528 (1997)

[文献書誌] Asakura Y., et al.: "Induction of HIV-1 specific mucosal immune responses by DNA vaccination." Scand.J.Immunol.46. 326-330 (1997)

[文献書誌] Toda S., et al.: "HIV-1 specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomea and inhibited by anti-interferon(IFN)-γ antibody." Immunology. 92. 111-117 (1997)

[文献書誌] Mor G., et al.: "Do DNA vaccines induce autoimmune disease?" Hum.Gene.Ther.8. 293-300 (1997)

[文献書誌] Tanabe S., et al.: "Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes." J.Immunol.159. 905-911 (1997)

[文献書誌] Mohri H., et al.: "Synthetic peptide from the V3 loop consensus motif with A potent anti-HIV activity inhibits ristocetin-mediated VWF-GPlb interaction" Peptide. 18. 1289-1293 (1997)

[文献書誌] Ishii N., et al.: "Genetic control of immune responses to HIV-1 env DNA vaccine." Microbiol.Immunol.41. 421-425 (1997)

[文献書誌] Okada E., et al.: "Intranasal immunization of a DNA vaccine with interleukin 12 and granulocyte macrophage colony stimulating factor(GM-CSF)expressing plasmids in liposomes induce strong mucosal and cell-mediated immune responses" J.Immunol.159. 3638-3647 (1997)

[文献書誌] Sasaki S., et al.: "A comparison of intranasal and intramuscular DNA vaccination against human immunodeficiency virus type 1 with monophosphoryl lipid A adjuvant." Infect.Immun.66. 823-826 (1998)

[文献書誌] Sasaki S., et al.: "Adjuvant effect of ubenimex on the responses induced by DNA vaccine for human immunodeficiency virus type-1" Clin.Exp.Immunol.111. 30-36 (1998)

[文献書誌] Xin K.-Q., et al.: "Intranasal administration of HIV-1 DNA vaccine with IL-2 expression plasmid enhances cell-mediated" Immunology. (in press). (1998)

[文献書誌] Sasaki S., et al: "Induction systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 adjuvant via intramuscular and intranasal routes." J.Virol.(in press). (1998)

[文献書誌] OKuda K., et al.: "Methods in molecular biology(ed.D.B.Iowire)." Humana press,Totowa,NJ.(in press), (1997)

[文献書誌] Sasaki S.& Okuda K.: "Methods in molecular biology(ed.D.B.Iowire)." Humana press,Totowa,NJ.(in press), (1997)

1997 年度実績報告書

奥田研爾横浜市立大学, 医学部, 教授 (40124862)