HIV Vaccine Development in Japan : Positive Immune Response and Its Progress

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1 ,**. The Japanese Society for AIDS Research The Journal of AIDS Research +1 HIV Vaccine Development in Japan : Positive Immune Response and Its Progress Including Reports from The +1th Annual Meeting of The Japanese Society for AIDS Research Vaccine Symposium + +, - - Masafumi TAKIGUCHI +, Takamasa UENO +, Tetsuro MATANO,, Kazuhiro MATSUO - and Mitsuo HONDA - +, - + Center for AIDS Research, Kumamoto University, Development of Microbiology, Graduate School of Medicine, The University of Tokyo - AIDS Research Center, National Institute of Infectious Diseases :HIV 0 : 2, 3*,**. HIV, WHO,**, -1 HIV HIV HIV + HIV HVI-+ HIV-+ HIV-+ : +0, 20.* +,- +,**. / 1 HIV-+, HIV AIDS - HIV-+ + HIV T CTL HIV HIV CTL CTL HIV HIV 2,,0

2 The Journal of AIDS Research Vol. 0 No.,,**. + HIV CTL HIV Nef HLA I CD2 T + HIV HIV CTL HIV HIV CTL T HIV T HIV T HIV HIV CTL CTL // /23 CTL// CTL/23 HIV-+ HLA-B* -/*+ IPLTEEAEL, - HLA-B-/ CTL,A HIV-+ CTL/23 HIV-+ CTL//,B IFN-g TNF-a CTL// HIV HIV CD-, - CTL// /23 Vd+ Vb+-.- Va+, Vb/.0 TCR +, TCR TCR T TCR CTL// TCR HIV CTL// TCR Vd+ HIV. HIV HIV CTL HIV CTL HIV HIV CTL HLA TCR HLA T HIV HIV CTL 2-,1

3 M Takiguchi et al : HIV Vaccine Development in Japan : Positive Immune Responses and Its Progress, CTL - CTL. HIV ex vivo 2.,2

4 The Journal of AIDS Research Vol. 0 No.,,**. HIV CD2 T CTL HIV HIV CTL HLA CTL T TCR HLA HIV HIV CTL TCR HIV CTL. A HIV B CTL// CTL/23 /+ Cr CTL// /23 CD-. HIV CD2. TCR A HLA-B-/ B HIV-+ C IL-, +,, Gag CTL +32* HIV-+ trial HIV-+ +33* HIV T CTL CTL,*** SHIV 23.0P HIV-+ SIV CTL CTL DNA SeV SHIV CTL SIVmac,-3 DNA Gag SeV SeV-Gag CTL HIV HIV CTL HIV. / 2 / SIV / - Gag CTL / SIV genome gag / + CTL dominant CTL wild-type SIV / CTL SIV CTL CTL DNA CTL Gag CTL / E 2/,3

5 M Takiguchi et al : HIV Vaccine Development in Japan : Positive Immune Responses and Its Progress CRF *+_AE HIV-+ BCG /, V- rbcg SHIV / CTL SIVmac,-3 Gag p// rbcg +30+ DIs 0 1 DNA HIV-+ Gag DIs iv Gag CTL 2 rbcg-sivgag +* mg, SC rdis-sivgag +* 0 pfu, IV SHIV SHIV C, BCG rbcg-gage rdis-gage prime-boost boost rdis, 0 BCG DIs BCG-Gag DIs-Gag SHIV CD. T HIV-+ gag BCG DIs 20 -*

6 The Journal of AIDS Research Vol. 0 No.,,**. BCG : *.+ mg, ID, DIs : +* 1 pfu, ID Gag DIs Gag boost 3 +* 1 rbcg-prime & rdis-boost rbcg Gag processing MHC class II pathway T priming rdis Gag MHC class I pathway Gag CTL rdis-sivgag, rbcg-sivgag rdis-sivgag prime-boost ++ +, rbcg priming T rbcg-gage prime & rdis-gage boost regimen GMP grade seed vaccine Gag seed vaccine approval Thai AIDS Vaccine Evaluation Group Clinical Investigation Brochure. HIV + NIH AIDS Bonnie Mathieson,**., NIH AIDS Adeno HIV Gag DNA Adeno/ SHIV23.0p Norman L. Letvin 2A SIV Mamu-A* *+ Mamu-A* *+ 2B David I. Watkins SHIV DNA Adeno / SIV + SHIV X. R/ SHIV SIV R/, SHIV23.0p HIV AIDS - Adeno/ SIV SIV SIV. preliminary Adeno 2* 21 -+

7 M Takiguchi et al : HIV Vaccine Development in Japan : Positive Immune Responses and Its Progress ῌ 1 BCG!"# $% ῌ 2A ῌ 2B 22 & -, '

8 The Journal of AIDS Research Vol. 0 No.,,**. + /* Adeno 1* Elispot -** -/* +* 0 PBMC,** Gag Elispot +21 -/ Adeno / +. Dr. N. Letvin Dr. D. Watkins Letvin SHIV SIV SHIV23.0 SIV Watkins HIV SIV R/ SIV SHIV + McMichael AJ, Rowland-Jones SL : Cellular immune responses to HIV. Nature.+* : 32* 321,,**+., Ueno T, Tomiyama H, Fujiwara M, Oka S, Takiguchi M : HLA class I-restricted recognition of an HIVderived epitope peptide by a human T cell receptor alpha chain having a Vdelta + variable segment. Eur J Immunol -- :,3+*,3+0,,**-. - Ueno T, Tomiyama H, Takiguchi M : Single T cell 23 --

9 M Takiguchi et al : HIV Vaccine Development in Japan : Positive Immune Responses and Its Progress receptor-mediated recognition of an identical HIVderived peptide presented by multiple HLA class I molecules. J Immunol +03 : ,,**,.. Matano T, Kano M, Nakamura H, Takeda A, Nagai Y : Rapid appearance of secondary immune responses and protection from acute CD. depletion after a highly pathogenic immunodeficiency virus challenge in macaques vaccinated with a DNA-prime/Sendai viral vector-boost regimen. J Virol 1/ : ,,**+. / Takeda A, Igarashi H, Nakamura H, Kano M, Iida A, Hirata T, Hasegawa M, Nagai Y, Matano T : Protective e$cacy of an AIDS vaccine, a single DNA-prime followed by a single booster with a recombinant replication-defective Sendai virus vector, in a macaque AIDS model. J Virol 11 : 31+* 31+/,,**-. 0 Tagaya I, Kitamura T, Sano Y : A new mutant of dermovaccinia virus. Nature +3, : -2+, Kitamura T, Kitamura Y, Tagaya I : Immunogenicity of an attenuated strain of vaccinia virus on rabbits and monkeys. Nature,+/ : , Matsuo K, Puthavathana P, Promkhatkaew D, Balachandra K, Ruxrungtham K, Hamano T, Sutthent R, Sittisombut N, Butraporn R, Sriwanthana B, Boonlong J, Izumi Y, Yamazaki S, Yamamoto N, Warachit P, Honda M : Japan s collaboration with Thailand in the development of HIV/AIDS vaccine. AIDS in ASIA, /0+ /03,,**.. 3 Hanke T, Samuel RV, Blanchard TJ, Neumann VC, Allen TM, Boyson JE, Sharpe SA, Cook N, Smith GL, Watkins DI, Cranage MP, McMichael AJ : E#ective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. J Virol 1- : 1/,., * Amara RR, Villinger F, Altman JD, Lydy SL, O Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL : Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science,3, : 03,,**+. ++ Izumi Y, Ami Y, Matsuo K, Someya K, Sata T, Yamamoto N, Honda M : Intravenous inoculation of replication-deficient recombinant vaccinia virus DIs expressing simian immunodeficiency virus gag controls highly pathogenic simian-human immunodeficiency virus in monkeys. J Virol 11 : +-,.2 +-,/0,,**-. +, Someya K, Xin KQ, Matsuo K, Okuda K, Yamamoto N, Honda M : A consecutive prime-boost vaccination of mice with simian immunodeficiency virus (SIV) gag/pol DNA and recombinant vaccinia virus strain DIs elicits e#ective anti-siv immunity. J Virol, in press,,**.. 3* -.