Elicitation of broad neutralizing antibodies to HIV-1 and development of infection rat model

• Project/Area Number: 21390135
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: SHIDA Hisatoshi 北海道大学, 遺伝子病制御研究所, 教授 (00144395)
• Co-Investigator(Kenkyū-buntansha): INOUE Makoto ディナベック株式会社, 研究開発部長 (30373541) ; SHIODA Tatsuo 大阪大学, 微生物病研究, 教授 (00187329)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: ワクチン / ウイルスベクター / ラットモデル / HIV-1 / CTL / 中和抗体 / センダイベクター / ワクシニアベクター / ラット / 感染モデル

Research Abstract

To develop HIV-1 vaccine, it is required to elicit both anti HIV-1 CTL and antibodies. In this study we unexpectedly found that vaccination regimen including priming with vaccinia LC16m8Δ expressing the env gene followed by boosting with sendai vector expressing the env gene elicited both anti HIV-1 CTL and antibodies.

Research Products

• [Journal Article] Geographic, Genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis) (2012)
  • Author(s): Saito A
  • Journal Title: J Gen Virol Volume: 93 Pages: 594-602
  • Peer Reviewed
• [Journal Article] TRIM5 α and Species Tropism of HIV/SIV (2012)
  • Author(s): Nakayama EE
  • Journal Title: Front Microbiol Volume: 3 Pages: 13-13
  • DOI: 10.3389/fmicb.2012.00013
  • Peer Reviewed
• [Journal Article] A proposal for a new HIV-1 DLS structural model (2012)
  • Author(s): Sakuragi JI
  • Journal Title: Nucleic Acids Res Volume: (In press)
  • Peer Reviewed
• [Journal Article] Role of human TRIM5αin intrinsic inmunity (2012)
  • Author(s): Nakayama EE
  • Journal Title: Front Microbiol Volume: 3 Pages: 97-97
  • DOI: 10.3389/fmicb.2012.00097
  • Peer Reviewed
• [Journal Article] Nuclear and CytoplasmicEffects of Human CRM1 on HIV-1Production in Rat Cells (2011)
  • Author(s): Mika Nagai-Fukataki, Takashi Ohashi, Iwao Hashimoto, Tominori Kimura, Yoshiyuki Hakata, Hisatoshi Shida
  • Journal Title: Genes to Cells Volume: 16 Pages: 203-216
• [Journal Article] MicroRNA Regulation of Glycoprotein B5R in Oncolytic Vaccinia Virus Reduces Viral Pathogenicity withoutImpairing its Antitumor Efficacy (2011)
  • Author(s): Mina Hikichi, Minoru Kidokoro, Takeshi Haraguchi, Hideo Iba, Hisatoshi Shida, Hideaki Tahara, Takafumi Nakamura
  • Journal Title: Mol.Ther Volume: 19 Pages: 1107-15
• [Journal Article] Flow cytometry based identification of simianimmunodeficiency virus Env-specific B lymphocytes (2011)
  • Author(s): Fofana IB, Colantonio AD, Reeves RK, Connole MA, Gillis JM, Hall LR, Sato S, Audin CR, Evans DT, Shida H, Johnson RP Johnson WE
  • Journal Title: J Immunol Methods Volume: 19 Pages: 75-85
• [Journal Article] Nuclear and Cytoplasmic Effects of Human CRM1 on HIV-1 Production in Rat Cells (2011)
  • Author(s): Mika Nagai-Fukataki, Takashi Ohashi, Iwao Hashimoto, Tominori Kimura, Yoshiyuki Hakata, Hisatoshi
  • Journal Title: Genes to Cells Volume: 16 Pages: 203-216
  • Peer Reviewed
• [Journal Article] The relationship between HIV-1 genome RNA dimerization, vinon maturation and infectivity (2011)
  • Author(s): Ohishi M
  • Journal Title: Nucleic Acids Res Volume: 39 Pages: 3404-17
  • Peer Reviewed
• [Journal Article] A Single Amino Acid of Hunan Immunodeficiency Virus Type 2 Capsid Protein Affects Conformation of Two External Loops and Viral Sensitivity to TRIM5alpha (2011)
  • Author(s): Miyamoto T
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Nuclear and Cytoplasmic Effects of Human CRMI on HIV-1 Production in Rat Cells (2011)
  • Author(s): Mika Nagai-Fukataki, Takashi Ohashi, Iwio Hashimoto, Tominori Kimura, Yoshiyuki Hakata, Hisatoshi Shida
  • Journal Title: Genes to Cells Volume: 16 Pages: 203-216
  • Peer Reviewed
• [Journal Article] The relationship between HIV-1 genome RNA dimerization, virion maturation and infectivity. (2011)
  • Author(s): Ohishi M, Shioda T
  • Journal Title: Nucleic Acids Research Volume: In press
  • Peer Reviewed
• [Journal Article] Provision of continuous maturation signaling to dendritic cells by RIG-Istimulating cytosolic RNA synthesis of Sendai virus. (2011)
  • Author(s): Okano S, Yonemitsu Y, Shirabe K, Kakeji Y, Maehara Y, Harada M, Yoshikai Y, Inoue M, Hasagawa M, Sueishi K.
  • Journal Title: J Immunol. Volume: 186 Pages: 1828-1839
  • Peer Reviewed
• [Journal Article] Inhibitory effect of human TRIM5 on HIV-1 production (2010)
  • Author(s): Xianfeng Zhang, Mariko Kondo, Jing Chen, Hiroyuki Miyoshi, HajimeSuzuki, Takashi Ohashi, Hisatoshi Shida
  • Journal Title: Microbes and Infection Volume: 12 Pages: 768-777
• [Journal Article] Inhibitory effect of human TRIM5α on HIV-1 production (2010)
  • Author(s): Xianfeng Zhang, Mariko Kondo, Jing Chen, Hiroyuki Miyoshi, Hajime Suzuki, Takashi Ohashi, Hisatoshi Shida
  • Journal Title: Microbes and Infection Volume: 12 Pages: 768-777
  • Peer Reviewed
• [Journal Article] Immunogenicity of newly constructed attenuated vaccinia strain LC16m8Δthat expresses SIV Gag protein (2009)
  • Author(s): Hajime Suzuki, Minoru Kidokoro, Ismael Ben Fofana, Takashi Ohashi, Tomotaka Okamura, Kazuhiro Matsuo, Naoki Yamamoto, Hisatoshi Shida
  • Journal Title: Vaccine Volume: 27 Pages: 966-971
• [Journal Article] Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages (2009)
  • Author(s): Hiroyuki Okada, Xianfeng Zhang, Ismael B Fofana, Mika Nagai, Hajime Suzuki, Takashi Ohashi and Hisatoshi Shida
  • Journal Title: Retrovirology Volume: 6 Pages: 43-43
• [Journal Article] Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages. (2009)
  • Author(s): Hiroyuki Okada, Xianfeng Zhang, Ismael B Fofana, Mika Nagai, Hajime Suzuki, Takashi Ohashi, Hisatoshi Shida
  • Journal Title: Retrovirology 6 Pages: 43-43
  • Peer Reviewed
• [Journal Article] Immunogenicity of newly constructed attenuated vaccinia strain LC16m 8Δ that expresses SIV Gag protein (2009)
  • Author(s): Hajime Suzuki, Minoru Kidokoro, Ismael Ben Fofana, Takashi Ohashi, Tomotaka Okamura, Kazuhiro Matsuo, Naoki Yamamoto, Hisatoshi Shida
  • Journal Title: Vaccine 27 Pages: 966-971
  • Peer Reviewed
• [Journal Article] Impact of a single amino acid in the variable region 2 of the old world monkey TRIM5a SPRY(B30.2)domain on anti-human immunodeficiency virus type 2 activity. (2009)
  • Author(s): Kono K
  • Journal Title: Virology 388 Pages: 160-8
  • Peer Reviewed
• [Presentation] Immunogenicity of LCl6m8△ Vaccinia Virus/Sendai Virus Vector Expressing the gp160 of HIV-1 and Effect of CD40Lm (2011)
  • Author(s): H.Shida
  • Organizer: AIDS VCCINE 2011
  • Place of Presentation: Convection CT (Thailand)
  • Year and Date: 2011-09-15
• [Presentation] Enhancement of CD40Lm on Vaccine Elicited Anti-HIV-1 Immunity (2011)
  • Author(s): Xianfeng Zhang, Tomoyoshi Sobue, Hisatoshi Shida
  • Organizer: IAS Conference on HIV Pathogenesis
  • Place of Presentation: Treatment and Prevention. Rome, Italy
  • Year and Date: 2011-07-06
• [Presentation] Immunogenicity of Lc16M8Δ Vaccinia Prime/Sendai Virus Vector Boost Targeting the Envelope Glycoprotein of HIV-1 and Contribution of CD40Lm (2011)
  • Author(s): Tomoyoshi Sobue, Shun-Ichi Makino, Xianfeng Zhang, Takashi Ohashi, Kazunori Kato, Tatsuo Shioda, Makoto Inoue, Mamoru Hasegawa, Hisatoshi Shida
  • Organizer: International Congress of Virology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan
• [Presentation] Immunogenicity of LC16m8Δ Vaccinia Virus/Sendai Virus Vector Expressing the gp160 of HIV-1 and Effect of CD40Lm AIDS VCCINE (2011)
  • Author(s): H. Shida
  • Place of Presentation: Bangkok Thailand
• [Presentation] 抗Env免疫誘導に対するCD40Lmの効果 (2010)
  • Author(s): 祖父江友芳、大橋貴、志田壽利
  • Organizer: 第24回日本エイズ第学会学術総会
  • Place of Presentation: 東京・グランドプリンスホテル高輪
  • Year and Date: 2010-11-26
• [Presentation] ラット細胞におけるHIV複製へのRNA輸送因子hCRM1の効果 (2009)
  • Author(s): 永井美佳、大橋貴、木村富紀、志田壽利
  • Organizer: 第57回日本ウイルス学会学術総会
  • Place of Presentation: 都市センターホテル東京
  • Year and Date: 2009-10-26
• [Presentation] ヒトTRIM5αによるHIV-1産生の抑制効果 (2009)
  • Author(s): 張険峰、大橋貴、志田壽利
  • Organizer: 第57回日本ウイルス学会学術総会
  • Place of Presentation: 都市センターホテル東京
  • Year and Date: 2009-10-26
• [Remarks]
  • URL: http://www.igm.hokudai.ac.jp/molvir
• [Patent(Industrial Property Rights)] ワクシニアウイルスベクターおよびセンダイウイルスベクターからなるプライム/ブーストワクチン用ウイルスベクター (2011)
  • Inventor(s): 志田壽利、井上誠,他
  • Industrial Property Rights Holder: 北海道大学,他
  • Filing Date: 2011-10-21
  • Overseas
• [Patent(Industrial Property Rights)] ワクシニアウイルスベクターおよびセンダイウイルスベクターからなるプライム/ブーストワクチン用ウイルスベクター (2010)
  • Inventor(s): 志田壽利、井上誠,他
  • Industrial Property Rights Holder: 北海道大学,他
  • Industrial Property Number: 2010-237954
  • Filing Date: 2010-10-22
• [Patent(Industrial Property Rights)] ワクシニアウイルスベクターおよびセンダイウイルスベクターからなるプライム/ブーストワクチン用ウイルスベクター (2010)
  • Inventor(s): 祖父江友芳, 志田壽利, 井上誠, 他
  • Industrial Property Rights Holder: 北海道大学デイナベック株式会社, 他
  • Industrial Property Number: 2010-237954
  • Filing Date: 2010-10-22