Establishment of marmoset model for elucidation of the pathogenesis of dengue hemorrhagic fever and development of new treatment

• Project/Area Number: 25293112
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Kurane Ichiro 国立感染症研究所, その他部局等, その他 (90278656)
• Co-Investigator(Kenkyū-buntansha): TAKASAKI TOMOHIKO 国立感染症研究所, ウイルス第一部, 室長 (20221351) ; MATSUTANI TAKAJI 和歌山県立医科大学, 医学部, 講師 (70372290) ; SUZUKI RYUJI 独立行政法人国立病院機構, 相模原病院臨床研究センター, 室長 (70373470)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 感染防御・制御 / デングウイルス / マーモセット

Outline of Final Research Achievements

Dengue fever is an important vector-borne virus disease in the world. Dengue hemorrhagic fever, a severe and fatal form of illness, is developed in some patients. There have been no animal models for dengue fever and dengue hemorrhagic fever, and the absence of animal models has hampered the understanding of the pathogenesis and the development of measures for prevention and treatment. High levels of viremia were detected in marmosets after inoculation with dengue virus. Antibody and T cell responses were similar to those detected in humans. High levels of neutralizing antibodies were detected after immunization with candidate live-attenuated dengue vaccine, and viremia was not detected after challenge with a wild strain of the same serotype. These results suggest that marmosets are an animal model suitable for the elucidation of the pathogenesis of dengue hemorrhagic fever and the development of vaccine and treatment.

Research Products

• [Journal Article] Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus. (2015)
  • Author(s): Moi, M.L., Ami, Y., Shirai, K., Lim, C.K., Suzaki, Y., Saito, Y., Kitaura, K., Saijo, M., Suzuki, R., Kurane, I. and Takasaki, T.
  • Journal Title: American Journal of Tropical Medicine and Hygiene Volume: 92(2) Pages: 370-376
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viremia and serotype cross-reactive antibody responses consistent with secondary infection of humans (2014)
  • Author(s): Moi, M.L., Takasaki, T., Omatsu, T., Nakamura, S., Katakai, Y., Ami, Y., Suzaki, Y., Saijo, M., Akari, H. and Kurane, I.
  • Journal Title: Journal of General Virology Volume: 95 Issue: 3 Pages: 591-600
  • DOI: 10.1099/vir.0.060384-0
  • Peer Reviewed / Open Access