Study for side effects of inactivated SARS-CoV vaccine.

• Project/Area Number: 22790444
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: IWATA Naoko 国立感染症研究所, 感染病理部, 主任研究官 (10360695)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,456,279 (Direct Cost: ¥3,427,907、Indirect Cost: ¥1,028,372); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥556,279 (Direct Cost: ¥427,907、Indirect Cost: ¥128,372); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 感染防御 / ワクチン / 動物モデル / ウイルス / 感染症

Research Abstract

Severe acute respiratory syndrome-related coronavirus (SARS-CoV) is an emerging pathogen that causes severe respiratory illness. Whole UV-inactivated SARS-CoV (UV-V), bearing multiple epitopes and proteins, is a candidate vaccine against this virus. However, whole inactivated SARS vaccine that includes nucleocapsid protein is reported to induce eosinophilic infiltration in mouse lungs after challenge with live SARS-CoV. In this study, an ability of Toll-like receptor (TLR) agonists to reduce the side effects of UV-V vaccination in a 6-month-old adult BALB/c mouse model was investigated, using the mouse-passaged Frankfurt 1 isolate of SARS-CoV. Immunization of adult mice with UV-V, with or without alum, resulted in partial protection from lethal doses of SARS-CoV challenge, but extensive eosinophil infiltration in the lungs was observed. By contrast, TLR agonists added to UV-V vaccine, including lipopolysaccharide, polyU, and poly (I:C) (UV-V+TLR), strikingly reduced excess eosinophilic infiltration in the lungs and induced lower levels of interleukin-4 and -13 and eotaxin in the lungs than UV-V-immunization alone.Additionally, microarray analysis showed that genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement, and the polarization of Th2 cells were up-regulated in UV-V- but not in UV-V+TLR-immunized mice. Rather, genes downstream of TLR3 and TLR4 were up-regulated in UV-V+TLR- compared with UV-V-immunized mice. These findings suggest that vaccine-induced eosinophil immunopathology in the lungs upon SARS-CoV infection can be avoided by the TLR agonists adjuvant.

Research Products

• [Journal Article] Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus. (2012)
  • Author(s): Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, Peters CJ, Couch RB
  • Journal Title: PLoS One Volume: 7(4)
  • Peer Reviewed
• [Journal Article] Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus. (2012)
  • Author(s): Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, Peters CJ, Couch RB.
  • Journal Title: PLoS One. Volume: 7 (4) Issue: 8
  • DOI: 10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492
  • Peer Reviewed
• [Journal Article] Association of major histocompatibility complex class I haplotypes with disease progression after simian immunodeficiency virus challenge in Burmese rhesus macaques (2012)
  • Author(s): Nomura, T., Yamamoto, H., Shiino, T., Takahashi, N., Nakane, T., Iwamoto, N., Ishii, H., Tsukamoto, T., Kawada, M., Matsuoka, S., Takeda, A., Terahara, K., Tsunetsugu-Yokota, Y., Iwata-Yoshikawa, N., Hasegawa, H., Sata, T., Naruse T.K., Kimura, A., Matano, T.
  • Journal Title: Journal of Virology Volume: (in press) Issue: 12 Pages: 6481-90
  • DOI: 10.1128/jvi.07077-11
  • Peer Reviewed
• [Presentation] ARS-CoV感染動物モデルを用いたUV不活化SARS-CoVの副反応発生機序について (2012)
  • Author(s): 岩田奈織子、永田典代、鈴木忠樹、佐藤由子、横田恭子、西條政幸、森川茂、長谷川秀樹
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-14
• [Presentation] SARS-CoV感染動物モデルを用いたUV不活化SARS-CoVの免疫効果と副反応について (2012)
  • Author(s): 岩田奈織子、永田典代、辻 隆裕、長谷川秀樹、佐藤由子、佐多徹太郎
  • Organizer: 第99回日本病理学会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] SARS-CoV感染動物モデルを用いたUV不活化SARS-CoVの副反応発生機序について (2012)
  • Author(s): 岩田奈織子、永田典代、鈴木忠樹、佐藤由子、横田恭子、西條政幸、森川茂、長谷川秀樹
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
• [Presentation] サル痘ウイルス感染後カニクイザルにおける劇症化の病態解析。 (2012)
  • Author(s): 永田典代、佐藤由子、岩田奈織子、鈴木忠樹、倉田毅、佐多徹太郎、長谷川秀樹
  • Organizer: 第101回日本病理学会
  • Place of Presentation: 東京
• [Presentation] BALB/cマウスを用いた脳炎関連フラビウイルスの病原性の比較。 (2012)
  • Author(s): 永田典代、岩田奈織子、早坂大輔、佐藤由子、小島朝人、佐多徹太郎、長谷川秀樹
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
• [Presentation] 新生仔マウスにおける新規ヒトカルジオウイルス(Saffold virus)の神経病原性の解析。 (2012)
  • Author(s): 小谷治、鈴木忠樹、Naeem Asif、岩田奈織子、中島典子、片野晴隆、田口文広、長谷川秀樹、清水博之、永田典代
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
• [Presentation] Interferon gamma protects adult BALB/c mice from lethal respiratory illness after mouseadapted SARS-CoV infection (2011)
  • Author(s): Noriyo Nagata, Naoko Iwata, Hideki Hasegawa, Yuko Sato, Shigeru Morikawa, Tetsutaro Sata
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] Immune response against EEV and IMV in non-human primates vaccinated with a highly attenuated smallpox vaccine LC16m8 and protection from lethal monkeypox (2011)
  • Author(s): Masayuki Saijo, Yasushi Ami, Yuriko Suzaki, Noriyo Nagata, Naoko Yoshikawa (Iwata), Hideki Hasegawa, Momoko Ogata, Shuetsu-Fukushi, Tetsuya Mizutani, Tetsutaro Sata, Ichiro Kurane, Shigeru Morikawa
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] SARS-CoV感染動物モデルを用いたUV不活化SARS-CoVの副反応について (2010)
  • Author(s): 岩田奈織子、永田典代、辻隆裕、長谷川秀樹、佐藤由子、横田恭子、宇田晶彦、水谷哲也、西條政幸、森川茂、佐多徹太郎
  • Organizer: 第58回日本ウイルス学会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08