Determination of the role of anti-flavivirus antibody in antibody-dependent enhancement infection of dengue virus

• Project/Area Number: 23790515
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: MOI Meng ling 国立感染症研究所, ウイルス第一部, 研究員 (40597499)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 感染防御・抑制 / 診断・治療 / 感染免疫 / 感染症 / ウイルス / ワクチン

Research Abstract

In this study the role of anti-flavivirus antibodies during antibody-dependent enhancement of dengue virus (DENV) infection was characterized by using FcγR-expressing cells. Infection-enhancement antibody enhances dengue virus (DENV) replication in FcγR-expressing cells, contributing to high levels of viral replication during secondary infection; a prelude of severe DENV illness. The neutralizing and infection-enhancement activity of antibodies after dengue virus (DENV) infection, Japanese encephalitis virus (JEV) infection and JE vaccination was determined in this study. Using FcγR-expressing cells, serum samples from the early phase of DENV infection exhibited ADE activity but serum samples from late phase of DENV infection exhibited DENV neutralizing activity. Serum sample from a JEV patient exhibited ADE activity during the late phase of JEV infection. Additionally, serum samples from JEV vaccinees exhibited DENV cross-reactive IgG antibodies after JEV vaccination, but neutralizing activity to DENV was absent. The results suggest that other than DENV, flavivirus infection and vaccination also induce cross-reactive antibodies to DENV but cross-neutralizing activity may be low or absent, implying a role of these anti-flavivirus antibodies during DENV infection.

Research Products

• [Journal Article] Efficacy of tetravalent dengue vaccine in Thai schoolchildren (2013)
  • Author(s): Meng Ling Moi
  • Journal Title: Lancet Volume: 381(9827) Pages: 1094-1094
  • Peer Reviewed
• [Journal Article] Detection of Dengue Virus Nonstructural Protein 1 (NS1) by using ELISA as a Useful Laboratory Diagnostic Method for Dengue Virus Infection of International Travelers (2013)
  • Author(s): Meng Ling Moi
  • Journal Title: Journal of Travel Medicine Volume: 20(3) Issue: 3 Pages: 185-193
  • DOI: 10.1111/jtm.12018
  • Peer Reviewed
• [Journal Article] Presence of Viral Genome in Urine and Development of Hematuria and Pathological Changes in Kidneys in Common Marmoset (Callithrix jacchus) after Inoculation with Dengue Virus (2013)
  • Author(s): Meng Ling Moi
  • Journal Title: Pathogens Volume: 2(2) Issue: 2 Pages: 357-363
  • DOI: 10.3390/pathogens2020357
  • Peer Reviewed
• [Journal Article] Determination of antibody concentration as main parameter in a dengue virus antibody-dependent enhancement assay using FcgR-expressing cells (2013)
  • Author(s): Moi Meng Ling
  • Journal Title: Archives of Virology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Dengue virus infection-enhancing activity of undiluted sera obtained from patients with secondary dengue virus infection (2013)
  • Author(s): Meng Ling Moi
  • Journal Title: Transactions of the Royal Society of Tropical Medicine and Hygiene Volume: 107(1) Issue: 1 Pages: 51-58
  • DOI: 10.1093/trstmh/trs007
  • Peer Reviewed
• [Journal Article] Dengue virus type-3 infection in a traveler returning from Benin to Japan. (2012)
  • Author(s): Ujiie M, Moi ML, Kobayashi T, Takeshita N, Kato Y, Takasaki T, Kanagawa S
  • Journal Title: Journal of Travel Medicine, Volume: 19,4 Pages: 255-257
• [Journal Article] Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus. (2012)
  • Author(s): Omatsu T, Moi ML, Takasaki T, Nakamura S, Katakai Y, Tajima S, Ito M, Yoshida T, Saito A, Akari H, Kurane I
  • Journal Title: Journal of Medical Primatology Volume: 41,5 Pages: 289-296
• [Journal Article] Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcγR-expressing cells (2012)
  • Author(s): Moi ML, Lim CK, Chua KB, Takasaki T, Kurane I
  • Journal Title: PLoS Neglected Tropical Diseases Volume: 6(2)
• [Journal Article] Demographic features of imported dengue fever and dengue haemorrhagic fever in Japan from 2006 to 2009 (2012)
  • Author(s): Takasaki T, Kotaki A, Tajima S, Omatsu T, Harada F, Lim CK, Moi ML, Ito M, Ikeda M, Kurane I
  • Journal Title: Dengue Bulletin Volume: 35 Pages: 217-222
• [Journal Article] 感染症迅速診断キットの有用性と限界:デング熱 (2012)
  • Author(s): Moi ML, 高崎智彦
  • Journal Title: 小児科 Volume: 53(4) Pages: 457-465
• [Journal Article] Dengue virus type-3 infection in a traveler returning from Benin to Japan (2012)
  • Author(s): Mugen Ujiie
  • Journal Title: Journal of Travel Medicine Volume: 19(4) Issue: 4 Pages: 255-257
  • DOI: 10.1111/j.1708-8305.2012.00617.x
  • Peer Reviewed
• [Journal Article] Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus (2012)
  • Author(s): Tsutomu Omatsu
  • Journal Title: Journal of Medical Primatology Volume: 41(5) Pages: 289-296
  • Peer Reviewed
• [Journal Article] Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcgR-expressing cells (2012)
  • Author(s): Meng Ling Moi
  • Journal Title: PLoS Neglected Tropical Diseases Volume: 6(2) Issue: 2 Pages: e1536-e1536
  • DOI: 10.1371/journal.pntd.0001536
  • Peer Reviewed
• [Journal Article] クロアチアにおけるデング熱の流行 (2011)
  • Author(s): Moi ML
  • Journal Title: Infectious Agents Surveillance Report Volume: 32 (6) Pages: 165-167
• [Journal Article] アフリカからのデング熱輸入例 (2011)
  • Author(s): Moi ML, Takasaki T, Iwagoe H, Sakamoto M, Kobayashi K, Ujiie M.
  • Journal Title: Infectious Agents Surveillance Report Volume: 32 (6) Pages: 164-165
• [Journal Article] Detection of higher levels of dengue viremia using FcγR-expressing BHK-21 cells than FcγR negative cells in secondary infection but not in primary infection. (2011)
  • Author(s): Moi ML, Lim CK, Kotaki A, Takasaki T, Kurane I.
  • Journal Title: Journal of Infectious Diseases Volume: 203(10) Pages: 1405-1414
• [Journal Article] Dengue virus isolation relying on antibody-dependent enhancement mechanism using FcγR-expressing BHK cells and a monoclonal antibody with infection-enhancing capacity. (2011)
  • Author(s): Moi ML, Lim CK, Tajima S, Kotaki A, Saijo M, Takasaki T, Kurane I.
  • Journal Title: Journal of Clinical Virology. Volume: 52(3) Pages: 225-230
• [Journal Article] Dengue maculopathy in a traveler (2011)
  • Author(s): Ujiie M, Moi ML, Takeda N.
  • Journal Title: American Journal of Tropical Medicine and Hygiene. Volume: 85(6) Pages: 965-966
• [Journal Article] Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viremia and demonstration of protective immunity. (2011)
  • Author(s): Omatsu T, Moi ML, Hirayama T, Takasaki T, Nakamura S, Tajima S, Ito M, Yoshida T, Saito A, Katakai Y, Akari H, Kurane I.
  • Journal Title: Journal of General Virology. Volume: 92 Pages: 2272-2280
• [Journal Article] Dengue maculopathy in a traveler (2011)
  • Author(s): Ujiie M, Moi ML, Takeda N
  • Journal Title: The American journal of tropical medicine and hygiene Volume: 85(6) Issue: 6 Pages: 965-966
  • DOI: 10.4269/ajtmh.2011.11-0120
  • Peer Reviewed
• [Journal Article] Dengue virus isolation relying on antibody-dependent enhancement mechanism using FcgammaR-expressing BHK cells and a monoclonal antibody with infection-enhancing capacity (2011)
  • Author(s): Moi ML, Lim CK, Tajima S, Kotaki A, Saijo M, Takasaki T, Kurane I
  • Journal Title: Journal of clinical virology Volume: 52(3) Issue: 3 Pages: 225-230
  • DOI: 10.1016/j.jcv.2011.07.009
  • Peer Reviewed
• [Journal Article] Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viremia and demonstration of protective immunity. (2011)
  • Author(s): Omatsu, T., Moi, M.L., Hirayama., T., Takasaki, T., Nakamura, S., Tajima, S., Ito, M., Yoshida, T., Saito, A., Katakai, Y., Akari, H. and Kurane, I
  • Journal Title: Journal of General Virology Volume: 92(Pt10) Issue: 10 Pages: 2272-2280
  • DOI: 10.1099/vir.0.031229-0
  • Peer Reviewed
• [Journal Article] Detection of higher levels of dengue viremia using FcgammaR-expressing BHK-21cells than FcgammaR-negative cells in secondary infection but not in primary infection (2011)
  • Author(s): Moi ML, Lim CK, Kotaki A, Takasaki T, Kurane I
  • Journal Title: Journal of infectious diseases Volume: 203(10) Issue: 10 Pages: 1405-1414
  • DOI: 10.1093/infdis/jir053
  • Peer Reviewed
• [Journal Article] アフリカからのデング熱輸入症例 (2011)
  • Author(s): Moi ML, Takasaki T, Iwagoe H, Sakamoto M, Kobayashi K, Ujiie M
  • Journal Title: Infectious agents surveillance report Volume: 32(6) Pages: 164-165
• [Journal Article] クロアチアにおけるデング熱の流行 (2011)
  • Author(s): Moi ML
  • Journal Title: Infectious agents surveillance report Volume: 32(6) Pages: 165-167
• [Presentation] Re-assessment of dengue neutralizing antibody and viremia titers in dengue patients using FcγR-expressing cells (2012)
  • Author(s): Moi ML, Lim CK, Saijo M, Takasaki T, Kurane I.
  • Organizer: The 61st Annual Meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: Atlanta, USA
• [Presentation] Dengue fever outbreak among Japanese construction workers returning from India (2012)
  • Author(s): Ujiie M, Moi ML, Kato Y, Kotaki A, Takeshita N, Kanagawa S, Takasaki T, Ohmagari N.
  • Organizer: The 61st Annual Meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: Atlanta, USA
• [Presentation] Role of antibodies in dengue infection and protective immunity during secondary infection of marmosets (2012)
  • Author(s): Moi ML, Omatsu T, Nakamura S, Takasaki T, Ami Y, Katakai Y, Suzaki Y, Akari H, Kurane I.
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] ウイルスRNA安定保存キットの評価, (2012)
  • Author(s): 小滝徹、モイメンリン、田島茂、高崎智彦.
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] マーモセットを用いたチクングンニヤウイルスの霊長類モデルの検討 (2012)
  • Author(s): 林昌宏、網康至、藤井克樹、北浦一孝、モイメンリン、白井顕治、小滝徹、須崎百合子、森川茂、西條政幸、鈴木隆二、倉根一郎、高崎智彦.
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Dengue vaccine development: re-assessment fo dengue neutralizing antibody and viremia titers using FcγR-expressing cells (2012)
  • Author(s): Moi ML, Lim CK, Saijo M, Takasaki T, Kurane I
  • Organizer: The 34th Naito Conference: Infection, immunity and their control for health
  • Place of Presentation: Hokkaido
• [Presentation] Serological evidence of the co-circulation of multiple dengue virus serotypes in Kuala Lumpur, Malaysia (2012)
  • Author(s): Azami NAM, Moi ML, Takasaki T, Salleh SA, Neoh HM, Othman Z, Shah SA, Kurane I, Jamal R.
  • Organizer: 13^<th> Asia-Pacific Congress on Clinical Microbiology and Infection.
  • Place of Presentation: Beijing, China
• [Presentation] Ocular complications associated with imported dengue fever (2012)
  • Author(s): Ujiie M, Moi ML, Kato Y, Kanagawa S, Ohmagari N, Takeshita N, Takasaki T
  • Organizer: 9 ^<th> Asia Pacific Travel Health Conference in conjunction with the 5^<th> Regional Meeting of the International Society of Travel Medicine.
  • Place of Presentation: Singapore
• [Presentation] Application of the dengue non-structural protein 1 (NS1) ELISA for the detection of dengue virus infection in travelers (2012)
  • Author(s): Moi ML, Omatsu T, Tajima S, Lim CK, Saijo M, Kurane I, Takasaki T.
  • Organizer: 9 ^<th> Asia Pacific Travel Health Conference in conjunction with the 5^<th> Regional Meeting of the International Society of Travel Medicine.
  • Place of Presentation: SingaporeMoi ML, Lim CK, Saijo M, Kurane I, Takasaki T
• [Presentation] デング熱診断サーベイランスのためのNS1抗原検出診断キット (2012)
  • Author(s): Moi ML, Lim CK, Saijo M, Kurane I, Takasaki T.
  • Organizer: 86^<th> Annual Meeting of the Japanese Association for Infectious Diseases
  • Place of Presentation: Nagasaki, Japan
• [Presentation] Re-assessment of dengue neutralizing antibody and viremia titers in dengue patients using FcgR-expressing cells (2012)
  • Author(s): Meng Ling Moi
  • Organizer: The 61st Annual Meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: アトランタ、アメリカ
• [Presentation] Dengue fever outbreak among Japanese construction workers returning from India (2012)
  • Author(s): Mugen Ujiie
  • Organizer: The 61st Annual Meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: アトランタ、アメリカ
• [Presentation] Role of antibodies in dengue infection and protective immunity during secondary infection of marmosets (2012)
  • Author(s): Meng Ling Moi
  • Organizer: The 60th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 大阪
• [Presentation] Dengue vaccine development: re-assessment fo dengue neutralizing antibody and viremia titers using FcγR-expressing cells (2012)
  • Author(s): Meng Ling Moi
  • Organizer: The 34th Naito Conference: Infection, immunity and their control for health
  • Place of Presentation: 北海道
• [Presentation] Ocular complications associated with imported dengue fever (2012)
  • Author(s): Mugen Ujiie
  • Organizer: 9 th Asia Pacific Travel Health Conference in conjunction with the 5th Regional Meeting of the International Society of Travel Medicine
  • Place of Presentation: シンガポール
• [Presentation] Application of the dengue non-structural protein 1 (NS1) ELISA for the detection of dengue virus infection in travelers (2012)
  • Author(s): Meng Ling Moi
  • Organizer: 9 th Asia Pacific Travel Health Conference in conjunction with the 5th Regional Meeting of the International Society of Travel Medicine
  • Place of Presentation: シンガポール
• [Presentation] デング熱診断サーベイランスのためのNS1抗原検出診断キット (2012)
  • Author(s): Meng Ling Moi
  • Organizer: 86th Annual Meeting of the Japanese Association for Infectious Diseases
  • Place of Presentation: 長崎
• [Presentation] Molecular diagnosis and analysis of imported Chikungunya virus strains, Japan, 2006-2010 (2011)
  • Author(s): Lim CK, Takasaki T, Moi ML, Kotaki A, Kurane I, Saijo M.
  • Organizer: The 60th Annual Meeting of the American Society for Tropical Medicine and Hygiene,
  • Place of Presentation: Philadelphia, PA
• [Presentation] Detection of higher levels of dengue viremia using FcγR-expressing BHK-21 cells than FcγR-negative cells in secondary infection but not in primary infection (2011)
  • Author(s): Moi ML, Lim CK, Kotaki A, Takasaki T, Kurane I.
  • Organizer: International Congress of Virology
  • Place of Presentation: 北海道
• [Presentation] Pathogenesis of epidemic chikungunya virus in nonhuman primates (2011)
  • Author(s): Lim CK, Ami Y, Fujii Y, Moi ML, Kitaura K, Kotaki A, Morikawa S, Saijo M, Suzuki R, Kurane I, Takasaki T
  • Organizer: International Congress of Virology
  • Place of Presentation: 北海道
• [Presentation] Antibody-dependent enhancement of dengue virus infection: revisit of antibody response and viremia in dengue patients using FcγR-expressing cells (2011)
  • Author(s): Moi ML, Lim CK, Ito M, Takasaki T, Kurane I.
  • Organizer: 45th Joint Working Conference on Immunology and Viral Diseases, US-Japan Cooperative Medical Science Program.
  • Place of Presentation: Stanford University, カリフォルニア, 米国
• [Presentation] Antibody-dependent enhancement of dengue virus infection: revisit of antibody response and viremia in dengue patients using FcγR-expressing BHK cells (2011)
  • Author(s): Moi ML, Lim CK, Kotaki A, Takasaki T, Kurane I.
  • Organizer: 45th Joint Working Conference on Immunology and Viral Diseases
  • Place of Presentation: Stanford University, California, USA
• [Presentation] Detection of higher levels of dengue viremia using FcγR-expressing BHK-21 cells than FcγR negative cells in serum samples from patients with secondary infection but not in those with primary infection (2011)
  • Author(s): Moi ML, Lim CK, Kotaki A, Takasaki T, Kurane I
  • Organizer: IV International Congress on Virology
  • Place of Presentation: Sapporo, Japan
• [Book] 臨床と微生物 (2013)
  • Author(s): Meng Ling Moi
  • Publisher: 近代出版
• [Book] 小児科：感染症迅速診断キットの有用性と限界 (2012)
  • Author(s): Meng Ling Moi
  • Publisher: 金原出版
• [Book] 国内発生はほとんどないが注目される感染症1-デング熱・出血熱. 小児感染症学 (2011)
  • Author(s): Moi ML, 高崎智彦
• [Book] 小児感染症学 （デング熱・出血熱） (2011)
  • Author(s): モイメンリン、高崎智彦
  • Publisher: 診断と治療社
• [Remarks]
  • URL: http://www0.nih.go.jp/vir1/NVL/papers_web/papers_vbv.htm
• [Remarks]
  • URL: https://sites.google.com/site/sherrymoi/
• [Remarks] 研究者論文リスト個人ウェブページ
  • URL: https://sites.google.com/site/moisherrye/
• [Remarks] 研究者論文リストPubmed
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=moi+ml
• [Remarks] 所属研究機関（ウイルス1部2室）の研究成果リスト
  • URL: http://www0.nih.go.jp/vir1/NVL/papers_web/papers_vbv.htm
• [Remarks] 所属研究機関（ウイルス1部）の研究成果リスト
  • URL: http://www.nih.go.jp/niid/ja/from-vir1/2645.html
• [Remarks]
  • URL: http://www0.nih.go.jp/vir1/NVL/papers_web/papers_vbv.htm