Title | Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Lu C-L, Murakowski DK, Bournazos S, Schoofs T, Sarkar D, Halper-Stromberg A, Horwitz JA, Nogueira L, Golijanin J, Gazumyan A, Ravetch JV, Caskey M, Chakraborty AK, Nussenzweig MC |
Journal | Science |
Volume | 352 |
Issue | 6288 |
Pagination | 1001-4 |
Date Published | 2016 May 20 |
ISSN | 1095-9203 |
Keywords | Animals, Antibodies, Neutralizing, Apoptosis, CD4-Positive T-Lymphocytes, Cell Line, HIV Antibodies, HIV Infections, HIV-1, Homeodomain Proteins, Humans, Immunization, Passive, Immunosuppression, Interleukin Receptor Common gamma Subunit, Mice, Mice, Inbred NOD, Mice, Mutant Strains, Receptors, IgG, Viral Load |
Abstract | 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. |
DOI | 10.1126/science.aaf1279 |
Alternate Journal | Science |
PubMed ID | 27199430 |
PubMed Central ID | PMC5126967 |
Grant List | UL1 TR000043 / TR / NCATS NIH HHS / United States AI081677-05 / AI / NIAID NIH HHS / United States UM1 AI100663 / AI / NIAID NIH HHS / United States P01 AI100148 / AI / NIAID NIH HHS / United States 8 UL1 TR000043 / TR / NCATS NIH HHS / United States F31 AI118555-01 / AI / NIAID NIH HHS / United States AI100148-02 / AI / NIAID NIH HHS / United States P01 AI081677 / AI / NIAID NIH HHS / United States / / Howard Hughes Medical Institute / United States F31 AI118555 / AI / NIAID NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States 1UM1 AI100663-01 / AI / NIAID NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm