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

TitleEnhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.
Publication TypeJournal Article
Year of Publication2016
AuthorsLu 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
JournalScience
Volume352
Issue6288
Pagination1001-4
Date Published2016 May 20
ISSN1095-9203
KeywordsAnimals, 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.

DOI10.1126/science.aaf1279
Alternate JournalScience
PubMed ID27199430
PubMed Central IDPMC5126967
Grant ListUL1 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

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