Induction of complement-mediated lysis of HIV-1 by a combination of HIV-specific and HLA allotype-specific antibodies.

HLA-specific antibodies generated by allo-immunization are supposed to be involved in the control of HIV infections by both the neutralizing capacity of HLA-specific antibodies (Abs) and HLA-specific Ab-dependent complement-mediated lysis (CML). We further characterized CML of HIV primary isolates induced by HLA-specific Abs. Although HIV-specific and HLA allo-type specific Abs induced only weak CML of HIV primary isolates, several combinations of HLA allo-type specific Abs with HIV-specific Abs could enhance CML significantly. Nevertheless, certain HLA-specific Abs did not improve but even inhibit CML of HIV, although the corresponding HLA molecules were present. Thus, our results emphasize a possible limitation of allo-immunization as a potential approach to induce protective immunity against HIV.

Complement and antibodies: a dangerous liaison in HIV infection?

Due to ongoing recombination and mutations, HIV permanently escapes from neutralizing antibody (nAb) responses of the host. By the masking of epitopes or shedding of gp120, HIV-1 further impedes an efficient neutralization by Abs. Therefore, nAbs responses of the host are chasing behind a rapidly evolving virus and mainly non-neutralizing antibodies (non-nAbs) are present in the host. At the same time, complement deposition on immune-complexed HIV may counteract the immune response by enhancing the infection. On the other hand, complement-mediated lysis is a putative effector mechanism to control viral replication. Here we review the complex interplay between complement, neutralizing and non-neutralizing Abs during HIV infection and discuss the contribution of Abs and complement in blocking versus enhancing the course of infection.