Complement-Mediated Antibody-Dependent Enhancement of Viral Infections

Enhancement of in vitro infection by immune antibodies was described for several viral diseases, first for the dengue and respiratory syncytial virus infections. Immune enhancement of viral infection can be connected with vaccine failures since vaccinated individuals who develop enhancing antibodies may have an exaggerated disease upon exposure to the virus. A part of the antibody-dependent enhancement is mediated by complement activation; this enhancement is mediated by antibodies against the immunodominant part of the transmembrane protein (gp41) of HIV. Binding of the enhancing antibodies results in deposition of complement proteins (C1q) and activation products of C4 and C3 on virus particles; interaction of these proteins with the type 2 complement receptor (CR2) and the C1q receptor facilitates attachment of the HIV virions to the target cells and leads to increased virus production in vitro and probable in vivo as well. Complement mediated antibody dependent enhancement (C-ADE) was demonstrated to be clinically relevant in HIV infection by the authors of the present chapter. C-ADE was found to develop shortly after HIV-infection concomitantly with seroconversion, and strongly correlate to viral load in the course of HIV disease. C-ADE can be detected more frequently in advanced stages of HIV infection and their appearance may herald progression of disease. Combination treatment by antiviral drugs (HAART) leads to the disappearance of C-ADE; sera of the HAART-treated patients may neutralize HIV even in the presence of complement, which can be infrequently detected in untreated patients. These findings indicate that study of C-ADE may have of crucial importance at development of HIV vaccines.