Induction of ex vivo-pulsed self dendritic cell vaccine against congenital toxoplasmosis

• Project/Area Number: 25460512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Shinshu University (2014-2015); Chiba University (2013)
• Principal Investigator: AOSAI Fumie 信州大学, 医学部, 委嘱講師 (80150316)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 先天性トキソプラズマ症 / トキソプラズマHSP70 / 樹状細胞ワクチン / 細胞傷害性T細胞(CTL) / T細胞ペプチドエピトープ / 細胞傷害性T細胞 (CTL) / T細胞ペピチドエピトープ / 樹状細胞(DC)ワクチン / トキソプラズマHSP70 (T.g.HSP70) / 細胞傷害性T細胞（CTL） / Th1防御免疫

Outline of Final Research Achievements

１．Toxoplasma gondii infection during pregnancy induced the intrauterine growth retardation in fetus. The influences of T. gondii infection on placenta and fetal liver were shown by analyzing their dendritic cell (DC) maturation and Th polarization.
2. Not only CD8+ but CD4+ cytotoxic T lymphocytes (CTL) specific for T. gondii-infected cells were induced by the vaccination with a virulent tachyzoite-specific HSP70 (T.g.HSP70) gene targeting peripheral DC. Adoptive transfer experiments revealed that the vaccine-induced CTL possessed protective roles for toxoplasmosis at both acute and chronic phases of infection. CTL peptide epitopes of T.g.HSP70 which bound to murine and human MHC molecules were analyzed.

Research Products

• [Journal Article] Successful treatment of toxoplasmic encephalitis early diagnosed by a polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two cases reports and review of the literature. (2015)
  • Author(s): Miyagi T, Itonaga H, Aosai F, Taguchi J, Norose K, Mochizuki K, Fujii H, Furumoto A, Ohama M, Karimata K, Yamanoha A, Taniguchi H, Sato S, Taira N, Moriuchi Y, Fukushima T, Masuzaki H, Miyazaki Y.
  • Journal Title: Transplant Infect Dis. Volume: 17 Issue: 4 Pages: 593-8
  • DOI: 10.1111/tid.12401
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] uman wound myiasis caused by Phormia regina and Sarcophaga haemorrhoidalis in Minia Governorate, Egypt. (2015)
  • Author(s): Abdel-Hafeez EH, Mohamed RM, Belal US, Atiya AM, Takamoto M, Aosai F.
  • Journal Title: Parasitol Res. Volume: 114 Issue: 10 Pages: 3703-9
  • DOI: 10.1007/s00436-015-4599-4
  • Peer Reviewed
• [Journal Article] トキソプラズマHSP70による樹状細胞成熟分化と防御免疫誘導 (2015)
  • Author(s): 青才文江
  • Journal Title: 信州医学雑誌 Volume: 63 Pages: 351-3
  • NAID: 130005105752
  • Acknowledgement Compliant
• [Journal Article] CTL induction by DNA vaccine with Toxoplasma gondii-HSP70 gene (2014)
  • Author(s): Chu D, Moroda M, Piao LX, Aosai F.
  • Journal Title: Parasitol Int. Volume: 63 Issue: 2 Pages: 408-16
  • DOI: 10.1016/j.parint.2014.01.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Congenital toxoplasmosis from a mother with type 2 diabetes mellitus: A case report (2014)
  • Author(s): Sato S, Nishida M, Nasu K, Narahara H, Norose K, Aosai F
  • Journal Title: J Obstet Gynaecol Res. Volume: 40 Issue: 11 Pages: 2158-61
  • DOI: 10.1111/jog.12477
  • Peer Reviewed / Open Access
• [Journal Article] Human Cystic Echinococcosis in the Nalut District of Western Libya: A Clinico-epidemiological Study (2014)
  • Author(s): Mohamed RM, Abdel-Hafeez EH, Belal US, Norose K, Aosai F
  • Journal Title: Tropical Medicine and Health Volume: 42 Issue: 4 Pages: 177-184
  • DOI: 10.2149/tmh.2014-16
  • NAID: 130004691065
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed / Open Access
• [Journal Article] Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients (2013)
  • Author(s): Sumi M, Aosai F, Norose K, Takeda W, Kirihara T, Sato K, Fujikawa Y, Shimizu I, Ueki T, Hirosima Y, Ueno M, Ichikawa N, Watanabe M, Kobayashi H.
  • Journal Title: International Journal of Hematology Volume: 98 Pages: 214-222
  • Peer Reviewed
• [Presentation] IL-17A deficiency downregulates protective immunity of hosts by Toxoplasma gondii HSP70 expression. (2015)
  • Author(s): Aosai Fumie, Takamoto Masaya
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] Peyer’s patches are the primary invasion sites of Toxoplasma gondii regardless of the host immune status. (2015)
  • Author(s): 光永哲也、Li Kein、Feng Xue、青才文江、野呂瀬一美
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学三鷹キャンパス（東京都三鷹市）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] 羊水検査で胎児感染が判明し，化学療法により重症化が予防できた先天性トキソプラズマ症不顕性感染例の1例 (2013)
  • Author(s): 佐藤新平、西田正和、古川雄一、山崎靖人、奈須家栄、楢原久司、野呂瀬一美、青才文江
  • Organizer: 第70回 九州連合産婦人科学会
  • Place of Presentation: 熊本市国際交流会館
• [Presentation] 羊水検査で胎児感染が判明し，化学療法により重症化が予防できた先天性トキソプラズマ症不顕性感染例の1例 (2013)
  • Author(s): 佐藤新平、西田正和、古川雄一、山崎靖人、奈須家栄、楢原久司、野呂瀬一美、青才文江
  • Organizer: 第83回 日本感染症学会西日本地方部会
  • Place of Presentation: 大阪国際会議場
• [Presentation] CTL induction by DNA vaccine with Toxoplasma gondii HSP 70 gene (2013)
  • Author(s): Chu D, Aosai F
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉幕張メッセ.
• [Book] 「トキソプラズマ症」感染症予防必携 第3版 (2015)
  • Author(s): 青才文江
  • Total Pages: 634
  • Publisher: 日本公衆衛生協会
• [Book] 「先天性トキソプラズマ症」新領域別症候群シリーズ『神経症候群』第2版 周産期障害 TORCH症候群 (2014)
  • Author(s): 青才文江
  • Total Pages: 911
  • Publisher: 日本臨床社
• [Book] 感染症予防必携 第3版 「トキソプラズマ症」 (2014)
  • Author(s): 青才文江 .
  • Publisher: 日本公衆衛生協会
• [Book] 微生物学・感染看護学 微生物から感染防止を考える 「血液や体液中に存在する微生物（５）マラリア原虫」 (2013)
  • Author(s): 青才文江
  • Total Pages: 197
  • Publisher: 医歯薬出版株式会社
• [Remarks] 千葉大学医学研究院・感染生体防御学