Development of vaccine against HIV/AIDS using a panel of neutralizing monoclonal antibodies.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591295
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: MATSUSHITA Shuzo 熊本大学, エイズ学研究センター, 教授 (00199788)
• Project Period (FY): 2009 – 2011
• Keywords: 感染症防御学 / 感染症 / 中和抗体 / 免疫学 / ウイルス / 内科

Research Abstract

We investigated induction of neutralizing antibody response against HIV-1 using a panel of neutralizing monoclonal antibodies. Among the panel we identified an antibody(0. 5d) that could alter envelope trimer conformation to enhance the neutralizing activity of the other antibodies. We induced high titer neutralizing antibodies against SF162 by immunizing rabbits with a gp120-0. 5d complex. However, the anti-sera did not show significant cross-neutralizing activities to the panel of HIV-1 primary isolates. Basic research on antigen presentation to B cell is crucial to obtain such a broad response because a cross-neutralizing antibody recognizes a conformational epitope.

Research Products

• [Journal Article] Open-Label Randomized Multicenter Selection Studyof Once Daily Antiretroviral Treatment Regimen Comparing Ritonavir-Boosted Atazanavir to Efavirenz with Fixed-Dose Abacavir and Lamivudine (2011)
  • Author(s): Honda, M., Ishisaka, M., Ishizuka, N., Kimura, S., Oka, S.
  • Journal Title: Intern Med Volume: 50 Pages: 699-705
  • Peer Reviewed
• [Journal Article] Small molecular CD4 mimics as HIV entry inhibitors (2011)
  • Author(s): Narumi, T., Arai, H., Yoshimura, K., Harada, S., Nomura, W., Matsushita, S., Tamamura. H.
  • Journal Title: Bioorg Med Chem Volume: 19 Pages: 6735-6742
  • Peer Reviewed
• [Journal Article] CD4mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist (2010)
  • Author(s): Narumi, T., Ochiai, C., Yoshimura, K., Harada, S., Tanaka, T., Nomura, W., Arai, H., Ozaki, T., Ohashi, N., Matsushita, S., Tamamura, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Pages: 5853-5858
  • Peer Reviewed
• [Journal Article] CD4 mimics targeting the mechanism of HIV entry (2010)
  • Author(s): Yamada, Y., Ochiai, C., Yoshimura, K., Tanaka, T., Ohashi, N., Narumi T., Nomura, W., Harada, S., Matsushita, S., Tamamura, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 20 Pages: 354-358
  • Peer Reviewed
• [Journal Article] HIV-1 evasion of a neutralizing anti-V3 antibody involves acquisition of a potential glycosylation site in V2 (2010)
  • Author(s): Hatada, M., Yoshimura, K., Harada, S., Kawanami, Y., Shibata, J., Matsushita S.
  • Journal Title: J. Gen. Virol Volume: 91 Pages: 1335-1345
  • Peer Reviewed
• [Journal Article] Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds (2010)
  • Author(s): Yoshimura, K., Harada, S., Shibata, J., Hatada, M., Yamada, Y., Ochiai, C., Tamamura, H., Matsushita, S.
  • Journal Title: J. Virol Volume: 84 Pages: 7558-7568
  • Peer Reviewed
• [Presentation] Cross-reactivity and crossneutralizing activity of monoclonal antibody(MAbs) to CD4-induced epitope of gp120 against HIV-1B, C, CRF_01 subtype viruses (2011)
  • Author(s): Ramirez, K, Maruta, Y., Kuwata, T., Yoshimura, K, Tamamura, H., Matsushita, S
  • Organizer: 第25回日本エイズ学会学術集会・総会
  • Place of Presentation: ハイアットリージェンシー東京.東京都
  • Year and Date: 2011-11-30
• [Presentation] HIV-1のV3領域に結合する中和抗体の遺伝子組換えによる小型化の試み (2011)
  • Author(s): 丸田泰広、桑田岳夫、クリステル.パオラ.ラミレス.バルデス、松下修三
  • Organizer: 第25回日本エイズ学会学術集会・総会
  • Place of Presentation: ハイアットリージェンシー東京.東京都
  • Year and Date: 2011-11-30
• [Presentation] Construction of neutralizing antibody fragments for efficient access to V3 epitope (2011)
  • Author(s): Maruta, S., Ramirez, K, Kuwata, T., Matsushita, S.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2011-10-20
• [Presentation] Novel CD4-induced monoclonal antibodies(MAbs) with cross-neutralizing activity against primary isolates of HIV-1 B and C subtypes (2011)
  • Author(s): Ramirez, K., Maruta, Y., Kuwata, T., Yoshimura, K., Tamamura, H., Matsuhsita, S.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2011-10-20
• [Presentation] Biased induction of neutralizing antibodies with particular specificity and gene usage in SIVsmH635FC-infected macaques (2011)
  • Author(s): Kuwata, T., Takaki, K., Matsushita, S.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2011-10-20
• [Presentation] Two-step escape pathway of the HIV-1 primary isolates induced by the in vitro selection of maraviroc (2011)
  • Author(s): Yoshimura, K., Harada, S., Hamaji, A., Matsushita, S.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2011-10-20
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada, S., Ishikawa, T., Hamaji, A., Matsushita, S., Yoshimura, K.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2011-10-20
• [Presentation] Isolation of potent neutralizing monoclonal antibodies against V3 loop from SIV-infected macaques (2011)
  • Author(s): Kuwata, T., Igarashi, T., Matsushita, S.
  • Organizer: AIDS Vaccine 2011
  • Place of Presentation: Bankok Convention Center, Bangkok, Thailand
  • Year and Date: 2011-09-12
• [Presentation] Maraviroc-resistant subtype B primary HIV-1 induced in vitro selection became highly sensitive to anti-gp120 neutralizing antibodies and autologous plasma IgG under high concentrations of the CCR5 inhibitor (2011)
  • Author(s): Yoshimura, K., Harada, S., Hamji, A., Matsushita, S.
  • Organizer: 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: The Auditorium Parco della Musica, Roma, Italy
  • Year and Date: 2011-07-19
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada, S., Ishikawa, T., Hamaji, A., Matsushita S., Yoshimura K.
  • Organizer: 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: The Auditorium Parco della Musica, Roma, Italy
  • Year and Date: 2011-07-19
• [Presentation] HIV陽性者のメンタルヘルスへのアプローチその2メンタルヘルス問題の「今」を考える:どのように捉え、どうアプローチすることが可能だろうか?～うつと依存症(薬物)を中心に (2010)
  • Author(s): 松下修三
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: グランドプリンスホテル高輪ザ・プリンス.東京都
  • Year and Date: 2010-11-26
• [Presentation] 共催シンポジウム2最新の情報を明日の臨床に生かす-Year in review 2010-「病態の研究と治療薬開発の未来」 (2010)
  • Author(s): 松下修三
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: グランドプリンスホテル高輪ザ・プリンス.東京都
  • Year and Date: 2010-11-25
• [Presentation] CCR5阻害剤maraviroc(MVC)耐性誘導によるEnvの変異が中和抗体感受性に及ぼす影響 (2010)
  • Author(s): 吉村和久、原田恵嘉、濱治有希、松下修三
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: グランドプリンスホテル高輪ザ・プリンス.東京都
  • Year and Date: 2010-11-24
• [Presentation] ラルテグラビルはHIV-1のin vitro馴化におけるEnv選択に影響する (2010)
  • Author(s): 原田恵嘉、濱治有希、松下修三、吉村和久
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: グランドプリンスホテル高輪ザ・プリンス.東京都
  • Year and Date: 2010-11-24
• [Presentation] Strategy to overcome neutralization of HIV-1 primary isolates (2010)
  • Author(s): Matsushita, S., Mouri, S., Harada, S., Yamada, Y., Tamamura, H., Yoshimura, K.
  • Organizer: 1^<1th> GCOE joint international Symposium Kumamoto AIDS Seminar
  • Place of Presentation: Hotel Nikko Kumamoto, Kumamoto
  • Year and Date: 2010-10-06
• [Presentation] Impact of a point mutation V2(L175P) in neutralization resistance mediated by functional trimer formation of Env (2010)
  • Author(s): Liu, M., Shibata, J., Harada, S., Takehisa, J., Yoshimura, K., Matsushita, S.
  • Organizer: AIDS Vaccine 2010
  • Place of Presentation: The Omni Hotel at CNN Center, Atlanta, USA
  • Year and Date: 2010-09-28
• [Presentation] CD4 mimetic compound-mediated enhancement of the neutralization activities of anti-V3 and CD4i monoclonal antibodies against the standard panel of primary isolates (2010)
  • Author(s): Matsushita, S., Mouri, S., Harada, S., Yamada, Y., Tamamura, H., Yoshimura, K.
  • Organizer: XVIII International AIDS Conference
  • Place of Presentation: The Reed Messe Wien, Vienna, Austria
  • Year and Date: 2010-07-18
• [Presentation] エンベロープの進化と中和抗体.シンポジウムHIV細胞侵入とその防御機構 (2009)
  • Author(s): 松下修三
  • Organizer: 第23回に本エイズ学会学術集会・総会
  • Place of Presentation: 名古屋国際会議場.愛知県名古屋市
  • Year and Date: 20091126-28
• [Presentation] 最近分離した7種の臨床HIV-1株を用いたin vitroラルテグラビル耐性ウイルス誘導 (2009)
  • Author(s): 原田恵嘉, 吉村和久, 松下修三
  • Organizer: 第23回日本エイズ学会学術集会・総会
  • Place of Presentation: 名古屋国際会議場.愛知県名古屋市
  • Year and Date: 2009-11-26
• [Presentation] 実験室HIV-1 R5株を用いたin vitro CCR5阻害薬(maraviroc)耐性ウイルス誘導の試み (2009)
  • Author(s): 石川哲也, 畑田万紀子, 原田恵嘉, 吉村和久, 松下修三
  • Organizer: 第23回に本エイズ学会学術集会・総会
  • Place of Presentation: 名古屋国際会議場.愛知県名古屋市
  • Year and Date: 2009-11-26
• [Presentation] 抗HIV-1V3抗体からの逃避過程で挿入されるV2領域の糖鎖が保存されるメカニズム-HIV-1の進化における耐性度と増殖能のバランスに関する考察- (2009)
  • Author(s): 畑田万紀子、吉村和久、原田惠嘉、松下修三
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル.東京都
  • Year and Date: 2009-10-26
• [Presentation] A primary R5 isolate undergoes different escape pathway during in vitro selection with low or high concentration of an anti-V3 monoclonal antibody (2009)
  • Author(s): Narahara, C., Hatada, M., Harada, S., Yoshimura, K, . Matsushita, S.
  • Organizer: AIDS Vaccine 2009
  • Place of Presentation: The Marriott Rive Gauche Conference Center Paris, France
  • Year and Date: 2009-10-20
• [Presentation] In vitro induction of HIV-1 resistant to a CCR5 (2009)
  • Author(s): Yoshimura, K., Matsushita, S.
  • Organizer: Kumamoto AIDS Seminar GCOE Joint International Symposium-Satellite Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2009-09-30
• [Presentation] Accumulation of multiple functional mutations in HIV-1 gp120 is involved in the development of neutralization escape under pressure of neutralizing antibody in vitro (2009)
  • Author(s): Matsushita, S.
  • Organizer: Kumamoto AIDS Seminar GCOE Joint International Symposium-Satellite Symposium
  • Place of Presentation: Aso Resort Granvilio Hotel. Aso, Kumamoto
  • Year and Date: 2009-09-30
• [Presentation] Mechanism of maintaining a glycan-insertion in HIV-1 gp120 V2 region under pressure of a potent neutralizing antibody in vitro (2009)
  • Author(s): Matsushita, S., Narahara, C., Nishida, Y., Honda, A., Harada, S., Yoshimura, K.
  • Organizer: 10th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Kumamoto
  • Year and Date: 2009-09-29
• [Presentation] Generation of an integrase inhibitor raltegravir resistant variants using recent primary isolates, X4, R5 and dual/mix HIV-1 (2009)
  • Author(s): Harada, S., Yoshimura, K., Matsushita, S.
  • Organizer: 10th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Kumamoto
  • Year and Date: 2009-09-29
• [Presentation] In vitro induction of HIV-1 resistant to a CCR5 antagonist maraviroc (2009)
  • Author(s): Yoshimura, K., Harada, S., Hatada, M., Matsushita, S.
  • Organizer: 10th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Kumamoto
  • Year and Date: 2009-09-28
• [Presentation] Mutations in gp120 of R5 HIV-1 laboratory isolate induced by the in vitro selection of maraviroc confer highly sensitive to anti-V3 monoclonal antibody (2009)
  • Author(s): Ishikawa, T., Yoshimura, K., Hatada, M., Harada, S., Matsushita, S.
  • Organizer: 10th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Kumamoto
  • Year and Date: 2009-09-28
• [Presentation] Mechanism of maintaining a glycan-insertion in HIV-1 gp120 V2 region under pressure of a potent neutralizing antibody in vitro (2009)
  • Author(s): Hatada, M., Yoshimura, K., Harada, S., Matsushita, S.
  • Organizer: 10th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto. Kumamoto
  • Year and Date: 2009-09-28
• [Presentation] Polyclonal antibody response against gp120 including antibodies to V3, CD4bs and CD4i epitopes account or broad neutralization (2009)
  • Author(s): Matsushita, S., Narahara, C., Morizono, M., Nishida, Y., Honda. Shibata, A., Harada, S., Yoshimura, K, .
  • Organizer: 5th Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Cape Town Convensition Center, Cape Town, South Africa
  • Year and Date: 2009-07-20
• [Presentation] HIV-1に対する中和単クローン抗体の治療応用に向けた基礎研究 (2009)
  • Author(s): 松下修三
  • Organizer: 第9回日本蛋白質化学学会
  • Place of Presentation: 熊本全日空ホテルニュースカイ.熊本市
  • Year and Date: 2009-05-20