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

摘要

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.