Passive immunization with polyclonal or monoclonal IgG antibodies has been used to for prevention or early post-exposure treatment of numerous infectious pathogens, particularly viruses such as Hepatitis A and B, Varicella-Zoster, Rabies and Respiratory Syncytial virus. Thus, the recent isolation of broadly neutralizing monoclonal antibodies (mAbs) against the HIV-1 has engendered interest in testing these antibodies for prevention or treatment of HIV-1 infection. Numerous preclinical studies in non-human primates demonstrate the ability of neutralizing mAbs to completely block SHIV infection when administered prior to, or shortly after, viral exposure. For prevention of infection in humans, potential advantageous characteristics of passive immunization with human mAbs include likely clinical safety and prolonged plasma concentrations, with potential to mediate protection for weeks or months after a single dose. In contrast to prevention, where mAbs need to interrupt a viral transmission event, mAbs administered in the setting of established HIV-1 infection face the obstacle of viral escape variants. Thus, combinations of mAbs may be required. A key question is whether antibody Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can lead to killing of HIV-1 infected cells and impact the cell associated viral reservoir. Clinical trials to address questions of HIV-1 prevention and treatment are underway.
CROI Conference
