1998 Fiscal Year Annual Research Report

微生物感染に対するDNA接種免疫法に関する研究

Research Project

Project/Area Number	10044308
Research Category	Grant-in-Aid for international Scientific Research
Section	Joint Research .
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)	PHANUPHAK Pr Thai Red Cross Society, Program on AIDS, Director HINKULA Jorm Karolinska Institute, Microbiology and Tu, Researcher WAHREN Britt Karolinska Institute, Microbiology and Tu, Professor 浜島健治横浜市立大学, 医学部, 助手 (00114611) 福島淳横浜市立大学, 医学部, 助手 (00181256)
Keywords	DNAワクチン / HIV-1 / インフルエンザ / 緑膿菌 / 感染モデル / SCIDマウス / HIV-1C型 / gag-pol
Research Abstract	本研究はHIV-1等の微生物感染症に対するDNAワクチンの開発が可能かどうかを国内では実験が困難である、霊長類や、その他の実験動物を使い、それらに投与した際の免疫応答を調べ、さらにモデル感染系による感染防御能を調べることにより詳細に検討する・ことを目的としている。今年度は、マウスを使った各種アジュバントの研究で、IL-12、GM-CSFの効果が確認された。また、リポゾーム、およびMono phosphoryl lipidAを併用すると、細胞性免疫、体液性免疫の両者とも上昇することがわかった。一方、HIVのワクチンとして、C型ウイルスに対するものが、アフリカ、南米、東南アジアで非常に重要であることがわかった。そこで今回我々は、このC型に対するenv、gag、pol、のワクチンを作製し、それらをマウスに免疫したさいの抗原性を確認した。また、envのDNAワクチンについては、A型、B型、E型も作製し、それらの交差反応性についても検討を行った。その結果、C型および、B型のマクロファージ感染性株のものが、交差反応性が高く、C型ワクチンの有効性が示唆された。 Karolinska研究所ではSCID/huマウスによる免疫と臨床分離株を含む種々のHIV-1を用いた感染防御実験を行い、B型のenvDNAワクチン免疫群である程度の感染防御が見られた。また、タイのウイルスに対するワクチンの有効性もマウスで確認した。

Research Products
(13 results)

All Other

All Publications (13 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.: "Induction 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 adjuvant." Infect.Immun.66・2. 823-826 (1998)
[Publications] Fukushima,N.: "Melittin,a met abostatic peptide inhibiting G_s activity." Peptides. 19・5. 811-819 (1998)
[Publications] Xin,K.-Q.: "Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA vaccine with interleukin-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] Putkonen,P.: "Immune 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 Vaccine." 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(in press)" Humana Press,Totowa,NJ., (1999)
[Publications] Sasaki,S.: "Methods in Molecular Biology: The use of immunologic adjuvants in DNA vaccine preparations (in press)" Humana Press,Totowa,NJ., (1999)

1998 Fiscal Year Annual Research Report

微生物感染に対するDNA接種免疫法に関する研究

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.: "Induction 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 adjuvant." Infect.Immun.66・2. 823-826 (1998)

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

[Publications] Xin,K.-Q.: "Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA vaccine with interleukin-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] Putkonen,P.: "Immune 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 Vaccine." 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(in press)" Humana Press,Totowa,NJ., (1999)

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

奥田研爾横浜市立大学, 医学部, 教授 (40124862)