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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

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  • Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan; Division of Experimental Animal Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan; Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan; College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan; National Institute of Infectious Diseases, Tokyo, Japan

Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus–antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV–antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV–antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV–antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV–antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV–antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells.

Author Notes

* Address correspondence to Ichiro Kurane or Tomohiko Takasaki, National Institute of Infectious Diseases, Tokyo, Japan. E-mails: kurane@nih.go.jp or takasaki@nih.go.jp

Financial support: This work was supported by Research on Emerging and Re-Emerging Infectious Diseases Grants H23-shinkou-ippan-010 and H26-shinkou-jitsuyouka-007 from the Ministry of Health, Labour and Welfare, Japan and Kiban B Grant-in-Aid for Scientific Research 25293112 and Young Scientists B Grant-in-Aid for Scientific Research 26870872 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Authors' addresses: Meng Ling Moi, Chang-Kweng Lim, Masayuki Saijo, and Tomohiko Takasaki, Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan, E-mails: sherry@nih.go.jp, ck@nih.go.jp, msaijo@nih.go.jp, and takasaki@nih.go.jp. Yasushi Ami and Yuriko Suzaki, Division of Experimental Animal Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan, E-mails: yami@nih.go.jp and ysuzaki@nih.go.jp. Kenji Shirai, Kazutaka Kitaura, and Ryuji Suzuki, Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan, E-mails: k.shirai0727@gmail.com, kitaura@nih.go.jp, and r-suzuki@sagamihara-hosp.gr.jp. Yuka Saito, Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan, and College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan, E-mail: saito-y@nih.go.jp. Ichiro Kurane, National Institute of Infectious Diseases, Tokyo, Japan, E-mail: kurane@nih.go.jp.

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