Endogenous, controlled expression of anti-HIV-1 broadly neutralizing antibody
Abstract
Recently, researchers have identified a number of anti-HIV broadly neutralizing antibodies (bNAbs), such as VRC01 and N6, capable of targeting a broad range of HIV-1 strains. Passive immunization using these patient-derived bNAbs could provide temporary protection but are limited by the short antibody half-life. While current gene transfer technology allows sustained bNAb expression, it lacks the ability to control bNAb production in vivo resulting in possible autoimmunity. To address this issue of achieving controlled bNAb expression in vivo, we hypothesize that bNAb expression from transduced Flu-specific B cells can be activated and modulated by subsequent Flu immunizations in the Flu-preimmunized animal. In this preliminary study, we have constructed a bNAb (N6 and VRC01) -expressing murine retroviral vector (MIGR) and successfully transduced Flu-specific primary B cells. Following transfusion of these cells into Flu-immunized recipient mice, we observed an anamnestic N6 antibody response with subsequent Flu immunizations.