Enhanced clearance of HIV-1–infected cells by broadly neutralizing antibodies against HIV-1 in vivo

CL Lu, DK Murakowski, S Bournazos, T Schoofs… - Science, 2016 - science.org
CL Lu, DK Murakowski, S Bournazos, T Schoofs, D Sarkar, A Halper-Stromberg, JA Horwitz
Science, 2016science.org
Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle.
In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-
1–infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by
passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects
of the antibody are not limited to free viral clearance and blocking new infection but also
include acceleration of infected cell clearance. Consistent with these observations, we find …
Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1–infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4+ T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1–infected cells.
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