Novel viral vector by using activation of innate immune responses

• Project/Area Number: 25670225
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: YASUTOMI YASUHIRO 独立行政法人医薬基盤研究所, 霊長類医科学研究センター, センター長 (90281724)
• Co-Investigator(Kenkyū-buntansha): WATANABE Kenta 山口大学, 共同獣医学部, 助教 (20582208)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 免疫 / ワクチン / 感染症 / ウイルスベクター / 結核 / HPIV2 / 自然免疫 / アジュバント

Outline of Final Research Achievements

We assessed the effectiveness of a novel mucosal vaccine using recombinant human parainfluenza type 2 virus (rHPIV2) as a vaccine vector. rHPIV2 showed the expression of inserted Ag in respiratory epithelial cells. M gene eliminated rHPIV2, which is replication-incompetent, incorporated cDNA of Ag85B gene from Mycobacterium bovis (rHPIV2-Ag85B) elicited Ag85B-specific immune responses. Moreover, rHPIV2-Ag85B showed protective effects against M.tuberculosis infection. We also constructed HN protein, which is receptor molecule to infection with respiratory epithelial cell, deleted rHPIV2. These findings provide evidence for the possibility of rHPIV2 as a novel mucosal vaccine vector.

Research Products

• [Journal Article] Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques. (2015)
  • Author(s): Fukuyama, Y., Yuki, Y., Katakai, Y., Harada, N., Takahashi, H., Takeda, S., Mejima, M., Joo, S., Kurokawa, S., Sawada, S., Shibata, H., Park, EJ., Fujihashi., K, Briles, D., Yasutomi, Y., Tsukada, H., Akiyoshi, K., Kiyono, H.
  • Journal Title: Mucosal Immunol. Volume: - Issue: 5 Pages: 1144-1153
  • DOI: 10.1038/mi.2015.5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of mycobacteria major secretion protein, Ag85B, on allergic inflammation in the lung (2014)
  • Author(s): Tsujimura Y, Inada H, Yoneda M, Fujita T, Matsuo K, Yasutomi Y
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: 9-9
  • DOI: 10.1371/journal.pone.0106807
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization. (2014)
  • Author(s): Watanabe K, Matsubara A, Kawano M, Mizuno S, Okamura T, Tsujimura Y, Inada H, Nosaka T, Matsuo K, Yasutomi Y.
  • Journal Title: Vaccine Volume: 32 Issue: 15 Pages: 1727-1735
  • DOI: 10.1016/j.vaccine.2013.11.108
  • Peer Reviewed
• [Journal Article] Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist. (2014)
  • Author(s): Kobiyama K, Aoshi T, Narita H, Kuroda E, Hayashi M, Tetsutani K, Koyama S, Mochizuki S, Sakurai K, Katakai Y, Yasutomi Y, Saijo S, Iwakura Y, Akira S, Coban C, Ishii KJ.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 8 Pages: 3086-3091
  • DOI: 10.1073/pnas.1319268111
  • Peer Reviewed
• [Journal Article] DNA vaccine expressing the non-structural proteins of hepatitis C virus diminishes the expression of HCV proteins in a mouse model (2013)
  • Author(s): Takeshi Wada, Michinori Kohara and Yasuhiro Yasutomi
  • Journal Title: Vaccine Volume: 31 Issue: 50 Pages: 5968-5974
  • DOI: 10.1016/j.vaccine.2013.10.037
  • Peer Reviewed
• [Journal Article] Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis. (2013)
  • Author(s): Kitagawa H, Kawano M, Yamanaka K, Kakeda M, Tsuda K, Inada H, Yoneda M, Sakaguchi T, Nigi A, Nishimura K, Komada H, Tsurudome M, Yasutomi Y, Nosaka T, Mizutani H.
  • Journal Title: PLoS One. Volume: 8 Issue: 7 Pages: 66614-66614
  • DOI: 10.1371/journal.pone.0066614
  • Peer Reviewed
• [Journal Article] Cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species. (2013)
  • Author(s): Shimozawa N, Ono R, Shimada M, Shibata H, Takahashi I, Inada H, Takada T, Nosaka T, Yasutomi Y.
  • Journal Title: Differentiation Volume: 85 Issue: 4-5 Pages: 131-139
  • DOI: 10.1016/j.diff.2013.02.004
  • Peer Reviewed
• [Journal Article] Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice (2013)
  • Author(s): Kazuko Tajiri, Nobutake Shimojo, satoshi Sakai, Tomoko Machino-Ohtsuka, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Yoshiko Tsujimura, Taizo Kimura, Akira Sato, Yasuhiro Yasutomi, Kazutaka Aonuma
  • Journal Title: Cardiovasc Drugs Ther Volume: 27(5) Issue: 5 Pages: 413-24
  • DOI: 10.1007/s10557-013-6464-y
  • Peer Reviewed
• [Journal Article] TRIM5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to monkey-tropic human immunodeficiency virus type 1 (2013)
  • Author(s): Saito A, Nomaguchi M, Kono K, Iwatani Y, Yokoyama M, Yasutomi Y, Sato H, Shioda T, Sugiura W, Matano T, Adachi A, Nakayama E, Akari H
  • Journal Title: J Gen Virol Volume: 94(Pt 6) Issue: 6 Pages: 1318-24
  • DOI: 10.1099/vir.0.050252-0
  • Peer Reviewed
• [Journal Article] Dynamics of cellular immune responses in the acute phase of dengue virus infection. (2013)
  • Author(s): Yoshida T, Omatsu T, Saito A, Katakai Y, Iwasaki Y, Kurosawa T, Hamano M, Higashino A, Nakamura S, Takasaki T, Yasutomi Y, Kurane I, Akari H.
  • Journal Title: Arch Virol. Volume: 158 Pages: 1209-1220
  • NAID: 120005474482
  • Peer Reviewed
• [Journal Article] TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models. (2013)
  • Author(s): Tougan T, Aoshi T, Coban C, Katakai Y, Kai C, Yasutomi Y, Ishii KJ, Horii T.
  • Journal Title: Hum Vaccin Immunother. Volume: 39 Pages: 283-290
  • Peer Reviewed
• [Journal Article] Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells (2013)
  • Author(s): Nomaguchi M, Yokoyama M, Kono K, Nakayama EE, Shioda T, Saito A, Akari H, Yasutomi Y, Matano T, Sato H, Adachi A
  • Journal Title: Microbes and Infection Volume: 15(1) Issue: 1 Pages: 56-65
  • DOI: 10.1016/j.micinf.2012.10.013
  • Peer Reviewed
• [Presentation] Suppressive effect of Mycobacteria major secretion protein, Ag85B, to innate immune response is depending on the interaction with RIG-I. (2014)
  • Author(s): Tsujimura Yusuke, Yasutomi Yasuhiro
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Intranasal immunization with recombinant vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed mycobacteria-specific immunity. (2013)
  • Author(s): Watanabe K, Matsuo K, Yasutomi Y.
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
• [Presentation] The recognition mechanisms of Mycobacteria major secretion protein, Ag85B, in vivo (2013)
  • Author(s): TSUJIMURA Yusuke, YASUTOMI Yasuhiro.
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
• [Presentation] インフルエンザウイルス感染におけるヘルパーT細胞（Th）の病態への関与 (2013)
  • Author(s): 保富康宏
  • Organizer: 日本臨床ウイルス学会
  • Place of Presentation: 倉敷
  • Invited
• [Presentation] ワクチン開発のストラテジー：HIVワクチン・結核ワクチ開発の経験から」ワクチン開発に必要な研究を取り巻く環境の重要性 (2013)
  • Author(s): 保富康宏
  • Organizer: 日本ワクチン学会
  • Place of Presentation: 津
  • Invited
• [Presentation] 抗酸菌分泌抗原を組み込んだ弱毒エイズウイルスの霊長類カニクイザルにおける細胞性免疫反応の解析 (2013)
  • Author(s): 岡村 智崇、松尾 和浩、保富 康宏.
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 神戸