Development of antibody-inducing vaccine models by analysis of B404 which neutralizes various SIV strains

• Project/Area Number: 26430091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kumamoto University
• Principal Investigator: Kuwata Takeo 熊本大学, エイズ学研究センター, 助教 (70346063)
• Co-Investigator(Renkei-kenkyūsha): MATSUSHITA Shuzo 熊本大学, エイズ学研究センター, 教授 (00199788) ; IGARASHI Tatsuhiko 京都大学, ウイルス研究所, 教授 (90467431)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: antibody / SIV / vaccine / HIV / 中和抗体 / アカゲザル / ワクチン

Outline of Final Research Achievements

SIV-infected macaques, which is an animal model of HIV infection, was used for analysis to develop antibody-inducing vaccines. Binding of potent anti-SIV neutralizing antibody B404 was not affected by point mutations on Env, and was suggested to require the structure of antigen-binding domain with negative charges. The biased induction of B404-class antibodies in macaques suggested the effect of host factors in antibody induction. Moreover, maturation of antibodies resulted in increase of neutralization activity against homologous virus, but did not associated with cross-neutralization activity against heterologous viruses

Research Products

• [Journal Article] Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors (2016)
  • Author(s): Alam, M., Kuwata, T., Shimura, K., Yokoyama, M., Ramirez Valdez, K. P., Tanaka, K., Maruta, Y., Oishi, S., Fujii, N., Sato, H., Matsuoka M. and Matsushita S.
  • Journal Title: Retrovirology Volume: 13 Issue: 1 Pages: 70-70
  • DOI: 10.1186/s12977-016-0304-7
  • NAID: 120005973385
  • Peer Reviewed / Open Access
• [Journal Article] Cross-Neutralization Activity of Single-Chain Variable Fragment (scFv) Derived from Anti-V3 Monoclonal Antibodies Mediated by Post-Attachment Binding (2016)
  • Author(s): Maruta, Y., Kuwata, T., Tanaka, K., Alam, M., Valdez, K. P., Egami, Y., Yoshiaki Suwa, Y., Morioka, H. and Matsushita, S.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 69 Issue: 5 Pages: 395-404
  • DOI: 10.7883/yoken.JJID.2015.667
  • NAID: 130005416280
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access
• [Journal Article] Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies (2016)
  • Author(s): Kuwata T, Enomoto I, Baba M, Matsushita S
  • Journal Title: Antimicrob Agents Chemother Volume: 60 Issue: 1 Pages: 437-450
  • DOI: 10.1128/aac.02285-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques (2015)
  • Author(s): Guo K, Halemano K, Schmitt K, Katuwal M, Wang Y, Harper MS, Heilman KJ, Kuwata T, Stephens EB, Santiago ML
  • Journal Title: Immunogenetics Volume: 67 Issue: 7 Pages: 355-370
  • DOI: 10.1007/s00251-015-0844-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complementary and synergistic activities of anti-V3, CD4bs and CD4i antibodies derived from a single individual can cover a wide range of HIV-1 strains. (2015)
  • Author(s): Ramirez, K.P., Kuwata, T., Maruta, Y, Tanaka K., Muntasir, A., Yoshimura, K., Matsushita, S.
  • Journal Title: Virology Volume: 475 Pages: 187-203
  • DOI: 10.1016/j.virol.2014.11.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] CD4+T細胞の分化に対するHIV感染とmiR125bの影響の検討 (2016)
  • Author(s): 郭悠、南留美、小松真梨子、高濱宗一郎、高濱正吉、桑田岳夫、山本政弘、松下修三
  • Organizer: 第30回日本エイズ学会学術集会・総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-11-24
• [Presentation] Dynamics of HIV-1 DNA in long-term treated patients with hematological co-morbidities (2016)
  • Author(s): Stanoeva K, Konig A, Fukuda A, Kawanami Y, Kuwata T, Satou Y, Matsushita S
  • Organizer: 第30回日本エイズ学会学術集会・総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-11-24
• [Presentation] Analysis and characterization of HIV-1 envelope glycoprotein in Japanese patients with recent diagnosis (2016)
  • Author(s): Thida W, Kuwata T, Alam M, Tanaka K, Maun M, Shimizu M, Kawanami Y and Matsushita S
  • Organizer: 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
• [Presentation] Construction, purification and analysis of neutralization potency of anti-V3 scFv’s against HIV-1 strains in vitro (2016)
  • Author(s): Mamun M, Maruta Y, Tanaka K, Alam M, Thida W, Kuwata T and Matsushita S
  • Organizer: 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
• [Presentation] Induction of antibodies, which belonged to the same class as broadly neutralizing antibody B404, in macaques infected with SIVsmH635FC (2016)
  • Author(s): Kuwata T, Sano M, Matsuoka S, Shimizu M, Miura T, Seki Y, Akari H, Matano T and Matsushita S
  • Organizer: 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
• [Presentation] PM1/CCR5 cells transduced with T312 Intrabody have survival advantage, if challenged with SF162 HIV-1 strain (2016)
  • Author(s): Alves G, Kuwata T, Tanaka Y, Matsushita S
  • Organizer: 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
• [Presentation] Post-attachment neutralization of a broad range of HIV-1 strains by the small antibody fragments targeting CD4-induced (CD4i) epitope (2016)
  • Author(s): Tanaka K, Kuwata T, Takahama S, Alam M, Maruta Y, Ramirez Valdez K P, Shimizu M, Kawanami Y and Matsushita S
  • Organizer: 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
• [Presentation] Post-attachment Neutralization of a Wide Range of HIV-1 Strains by Anti-CD4i Single Chain Variable Fragment (scFv) (2016)
  • Author(s): Tanaka K, Kuwata T, Maruta Y, Ramirez Valdez K P, Alam M, Kawanami Y, Matsushita S
  • Organizer: HIVR4P 2016
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-10-17
  • Int'l Joint Research
• [Presentation] HIV proviral DNA quantification in a cohort of Japanese patients on long-term ART (2016)
  • Author(s): Stanoeva K, Konig A, Fukuda A, Kawanami Y, Kuwata T, Satou Y, Matsushita S
  • Organizer: 2016 Towards an HIV Cure Symposium
  • Place of Presentation: Durban, South Africa
  • Year and Date: 2016-07-16
  • Int'l Joint Research
• [Presentation] Incompatibility of HIV-1 Resistance to Both Cenicriviroc and Neutralizing Antibodies (2016)
  • Author(s): Kuwata T, Enomoto I, Baba M and Matsushita S
  • Organizer: The annual Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-02-22
  • Int'l Joint Research
• [Presentation] Impact of gp41 mutations on resistance to B404, a broad neutralizing antibody reactive against a conformational epitope of SIV gp120 (2015)
  • Author(s): Kuwata T, Shimizu M, Matsushita S
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22
• [Presentation] Impact of gp41 mutations for escape from a broad neutralizing antibody against SIV (2015)
  • Author(s): Kuwata T, Shimizu M, Matsushita S
  • Organizer: 16th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-07
• [Presentation] 強力な抗SIV中和抗体B404からの逃避メカニズムの解析 (2014)
  • Author(s): 桑田岳夫、松下修三
  • Organizer: 第28回日本エイズ学会学術集会・総会
  • Place of Presentation: 大阪国際会議場（大阪府北区）
  • Year and Date: 2014-12-03 – 2014-12-05
• [Presentation] Mutations in gp41 is Critical to Escape from B404, a Broad Neutralizing Antibody Against SIV, Which Recognizes a V3/V4 Conformational Epitope (2014)
  • Author(s): Takeo Kuwata, Kazuhisa Yoshimura, Fan Wu, Ilnour Ourmanov, Vanessa M. Hirsch, Masaru Yokoyama, Hironori Sato and Shuzo Matsushita
  • Organizer: 32nd Annual Symposium on Nonhuman Primate Models for AIDS
  • Place of Presentation: The Nines Hotel (Portland, Oregon, USA)
  • Year and Date: 2014-11-11 – 2014-11-14
• [Presentation] SIVサル・モデルを用いた中和抗体の解析 (2014)
  • Author(s): 桑田岳夫
  • Organizer: 第17回日本レトロウイルス研究会夏期セミナー
  • Place of Presentation: 伊豆山研修センター(静岡県熱海市)
  • Year and Date: 2014-07-03 – 2014-07-05
• [Remarks] 松下プロジェクト研究室 - 熊本大学エイズ学研究センター
  • URL: http://matsushita-lab.jp
• [Remarks] 熊本大学 エイズ学研究センター 松下プロジェクト研究室
  • URL: http://matsushita-lab.kumamoto-univ.jp