1998 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	09670293
Research Institution	Yokohama City University
Principal Investigator	奥田研爾横浜市立大学, 医学部, 教授 (40124862)
Co-Investigator(Kenkyū-buntansha)	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, 教授 (00184028)
Keywords	DNAワクチン / HIV-1 / Th1細胞 / IL-12 / gP160 / 粘膜免疫
Research Abstract	HIV、リステリア等の細胞内寄生体に対する感染防御に最も重要な免疫反応は、Th1を主体とした細胞性免疫反応であるが、粘膜表面上の分泌型IgAの誘導もまた重要であることが明らかになりつつある。今回の研究は、その双方の免疫応答を惹起することが可能かどうかを検討することであった。その応用への一つのモデルとして、我々の有するHIV,緑膿菌,インフルエンザウイルスワクチンの系を利用し、IL-12,IFN-γやB7プラスミドをワクチンと共に注入することにより、Th1タイプ反応を主体とするこれらの病原体に対する特異的免疫反応を、さらに増強できることが判明した。次に、インフルエンザM及び、NP抗原のDNAワクチンを注入した後に、各々免疫したマウスに緑膿菌又は、インフルエンザウイルスを注入し感染させる、いわゆる、チャレンジ実験を実施したところ、いずれの場合も完全ではないが非免疫グループに対し、有為な差で感染防御が増加することが判明した。更に、IL-12,IL-2,及びGM-CSFのDNAのexpressionプラスミドを注入することにより、DNAワクチンの免疫増強作用が見られた。今回の実験の結果、これらの方法により病原体に対する有効な防御能が得られることが判明したが、次の段階として安全性、更に大型動物による有効性等の検討が必要と思われる。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Sasaki,S.: "The search for a potent DNA vaccine against AIDS : The enhancement of immunogenicity by chemical and genetic adjuvants." Anticancer.Research. 18. 3907-3916 (1998)
[Publications] Sasaki,S.: "Adjuvant effect of ubenimex on the responses induced by DNA vaccine for human immunodeficiency virus type-1." Clin.Exp.Immunol.111. 30-36 (1998)
[Publications] Sasaki,S.: "lnduction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes." J.Virol.72・8. 4931-4939 (1998)
[Publications] Sasaki,S.: "A comparison of intranasal and intramuscular DNA vaccination against human immunodeficiency virus type 1 with monophosphoryl lipid A sdjuvant." Infect.Immun.66・2. 823-826 (1998)
[Publications] Fukushima,N.: "Melittin,a metabostatic peptide inhibiting G_s activity." Peptides. 19・5. 811-819 (1998)
[Publications] Xin,K.-Q.: "Intranasal administ ration of human immunodeficiency virus type-1(HIV-1)DNA vaccine with int erleukin-2 expression plasmid enhances cell-mediated immunity against HIV-1." Immunology. 94. 438-444 (1998)
[Publications] Hamajima,K.: "Intranasal administration of HIV-DNA vaccine formulated with a polymer,carboxymethylcellulose,augments mucosal antibody production and cell-mediated immune response." Clin.Immunol.Immunopath.88・2. 205-210 (1998)
[Publications] Ando,N.: "Differential gene expression of TGF-β isoforms and TGF-β receptors during the first trimester of pregnancy at the human maternal-fet al interface." Am.J.Reprod.Immunol.40・8. 48-56 (1998)
[Publications] Miyajima,Y.: "Long-range effect of mutation of calcium binding asparates on the catalytic activity of alkaline protease from Psudomonas aeruginosa." J.Biochem.123. 24-27 (1998)
[Publications] You,Z.: "Induction of entry into the stationary growth phase in Pseudomonas aeruginosa by N-acylhomoserine lactone." FEMS Microbiol.Lett.164. 99-106 (1998)
[Publications] Putkonen,P.: "lmmune responses but no protection against SHIV by gene-gun delivery of HIV-1 DNA followed by recombinant subunit protein boosts." Virology. 250. 293-301 (1998)
[Publications] Sasaki,S.: "Genes that induce immunity-DNA vaccines." Virology. 43. 191-200 (1999)
[Publications] Xin,K.-Q.: "IL-15 Expression Plasmid Enhances Cell-Mediated Immunity Induced by an HIV-1 DNA Vaccuine." Vaccine. 171. 858-868 (1999)
[Publications] Lu,Y.: "Macrophage inflammatory protein-1α(MIP-1α)expression plasmid enhances DNA vaccine-induced immune response against HIV-1." Clin.Exp.Immunol.115. 335-341 (1999)
[Publications] Okuda,K.: "Methods in Molecular Biology : Cytokine adjuvants for DNA vaccine" Humana Press,Totowa,NJ.(in press), (1999)
[Publications] Sasaki,S.: "Mcthods in Molecular Biology : the use of immunologic adjuvants in DNA vaccine preparations" Humana Press,Totowa,NJ.(in press), (1999)

1998 Fiscal Year Annual Research Report

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

Principal Investigator

奥田 研爾 横浜市立大学, 医学部, 教授 (40124862)

Research Products

[Publications] Sasaki,S.: "The search for a potent DNA vaccine against AIDS : The enhancement of immunogenicity by chemical and genetic adjuvants." Anticancer.Research. 18. 3907-3916 (1998)

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

[Publications] Sasaki,S.: "lnduction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes." J.Virol.72・8. 4931-4939 (1998)

[Publications] Sasaki,S.: "A comparison of intranasal and intramuscular DNA vaccination against human immunodeficiency virus type 1 with monophosphoryl lipid A sdjuvant." Infect.Immun.66・2. 823-826 (1998)

[Publications] Fukushima,N.: "Melittin,a metabostatic peptide inhibiting G_s activity." Peptides. 19・5. 811-819 (1998)

[Publications] Xin,K.-Q.: "Intranasal administ ration of human immunodeficiency virus type-1(HIV-1)DNA vaccine with int erleukin-2 expression plasmid enhances cell-mediated immunity against HIV-1." Immunology. 94. 438-444 (1998)

[Publications] Hamajima,K.: "Intranasal administration of HIV-DNA vaccine formulated with a polymer,carboxymethylcellulose,augments mucosal antibody production and cell-mediated immune response." Clin.Immunol.Immunopath.88・2. 205-210 (1998)

[Publications] Ando,N.: "Differential gene expression of TGF-β isoforms and TGF-β receptors during the first trimester of pregnancy at the human maternal-fet al interface." Am.J.Reprod.Immunol.40・8. 48-56 (1998)

[Publications] Miyajima,Y.: "Long-range effect of mutation of calcium binding asparates on the catalytic activity of alkaline protease from Psudomonas aeruginosa." J.Biochem.123. 24-27 (1998)

[Publications] You,Z.: "Induction of entry into the stationary growth phase in Pseudomonas aeruginosa by N-acylhomoserine lactone." FEMS Microbiol.Lett.164. 99-106 (1998)

[Publications] Putkonen,P.: "lmmune responses but no protection against SHIV by gene-gun delivery of HIV-1 DNA followed by recombinant subunit protein boosts." Virology. 250. 293-301 (1998)

[Publications] Sasaki,S.: "Genes that induce immunity-DNA vaccines." Virology. 43. 191-200 (1999)

[Publications] Xin,K.-Q.: "IL-15 Expression Plasmid Enhances Cell-Mediated Immunity Induced by an HIV-1 DNA Vaccuine." Vaccine. 171. 858-868 (1999)

[Publications] Lu,Y.: "Macrophage inflammatory protein-1α(MIP-1α)expression plasmid enhances DNA vaccine-induced immune response against HIV-1." Clin.Exp.Immunol.115. 335-341 (1999)

[Publications] Okuda,K.: "Methods in Molecular Biology : Cytokine adjuvants for DNA vaccine" Humana Press,Totowa,NJ.(in press), (1999)

[Publications] Sasaki,S.: "Mcthods in Molecular Biology : the use of immunologic adjuvants in DNA vaccine preparations" Humana Press,Totowa,NJ.(in press), (1999)

奥田研爾横浜市立大学, 医学部, 教授 (40124862)