The mechanism of ADE

S58941418 陳俊良

• ADE has been proposed as an underlying pathogenic mechanism of DHF/ DSS.

• It often occurs in patients with second, heterotypic DENV infections or in infants with maternally transferred dengue immunity.

1. ADE occurs because preexisting subneutralizing antibodies

2. The infecting DENV form complexes that bind to Fc receptor-bearing cells

3. Leading to increased virus uptake and replication

Antibody-dependent enhancement (ADE)

• ADE of DENV-2 infection has also been demonstrated in monkeys infused with a human dengue immune serum.

ND/SK: bind to human and mouse IgGIBN: can’t bind to human and mouse IgG

Antibody-dependent enhancement of infection by murine serum

B. Raji-1 (DC-SIGN) cells:has been shown to facilitate DENVinfection by a mechanism different from ADE

C. The difference in ADE activities among the different DENV serotypes was probably due to sequence variations in the antibody-binding sites.

in vitro IgG 1A5: chimpanzee–human chimeric IgG1 mAbs

in vivo

L-NIL, a specific inhibitor of iNOS

Primary DHF Primary DHF

2nd DHF 2nd DHF