PMID- 32665438
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20210121
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 117
IP  - 30
DP  - 2020 Jul 28
TI  - Quantifying the contribution of Fc-mediated effector functions to the antiviral 
      activity of anti-HIV-1 IgG1 antibodies in vivo.
PG  - 18002-18009
LID - 10.1073/pnas.2008190117 [doi]
AB  - In combating viral infections, the Fab portion of an antibody could mediate virus 
      neutralization, whereas Fc engagement of Fc-gamma receptors (FcgammaRs) could mediate an 
      array of effector functions. Evidence abounds that effector functions are 
      important in controlling infections by influenza, Ebola, or HIV-1 in animal 
      models. However, the relative contribution of virus neutralization versus 
      effector functions to the overall antiviral activity of an antibody remains 
      unknown. To address this fundamental question in immunology, we utilized our 
      knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline 
      (DeltaVL) in infected animals given a wild-type (WT) anti-HIV-1 immunoglobulin G1 
      (IgG1) versus those given a Fc-Null variant of the same antibody. In three 
      independent experiments in HIV-1-infected humanized mice and one pivotal 
      experiment in simian-human immunodeficiency virus (SHIV)-infected rhesus 
      macaques, an earlier and sharper decline in viral load was consistently detected 
      for the WT antibody. Quantifications of the observed differences indicate that 
      Fc-mediated effector functions accounted for 25-45% of the total antiviral 
      activity in these separate experiments. In this study, Fc-mediated effector 
      functions have been quantified in vivo relative to the contribution of virus 
      neutralization mediated by the Fab.
CI  - Copyright (c) 2020 the Author(s). Published by PNAS.
FAU - Wang, Pengfei
AU  - Wang P
AUID- ORCID: 0000-0003-2454-7652
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Gajjar, Mili R
AU  - Gajjar MR
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Yu, Jian
AU  - Yu J
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Padte, Neal N
AU  - Padte NN
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Gettie, Agegnehu
AU  - Gettie A
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Blanchard, James L
AU  - Blanchard JL
AD  - Tulane National Primate Research Center, Tulane University, Covington, LA 70433.
FAU - Russell-Lodrigue, Kasi
AU  - Russell-Lodrigue K
AUID- ORCID: 0000-0003-3719-0779
AD  - Tulane National Primate Research Center, Tulane University, Covington, LA 70433.
FAU - Liao, Laura E
AU  - Liao LE
AUID- ORCID: 0000-0001-6069-2633
AD  - Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, 
      NM 87545.
FAU - Perelson, Alan S
AU  - Perelson AS
AUID- ORCID: 0000-0002-2455-0002
AD  - Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, 
      NM 87545.
FAU - Huang, Yaoxing
AU  - Huang Y
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032.
FAU - Ho, David D
AU  - Ho DD
AD  - Aaron Diamond AIDS Research Center, Columbia University Vagelos College of 
      Physicians and Surgeons, New York, NY 10032; dh2994@cumc.columbia.edu.
LA  - eng
GR  - R01 OD011095/OD/NIH HHS/United States
GR  - P01 AI131365/AI/NIAID NIH HHS/United States
GR  - R01 AI145645/AI/NIAID NIH HHS/United States
GR  - P51 OD011104/OD/NIH HHS/United States
GR  - R01 AI028433/AI/NIAID NIH HHS/United States
GR  - R01 AI129802/AI/NIAID NIH HHS/United States
GR  - R01 AI134328/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200714
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (HIV Antibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
SB  - IM
CIN - doi: 10.1073/pnas.2008236117
MH  - Animals
MH  - Antibodies, Neutralizing/immunology
MH  - Disease Models, Animal
MH  - HIV Antibodies/*immunology
MH  - HIV Infections/*immunology/*metabolism/virology
MH  - HIV-1/*immunology
MH  - Host-Pathogen Interactions/immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Neutralization Tests
MH  - Receptors, IgG/*metabolism
PMC - PMC7395461
OTO - NOTNLM
OT  - HIV-1 dynamics
OT  - antibody
OT  - effector functions
OT  - in vivo quantification
OT  - neutralization
COIS- Competing interest statement: J.Y., Y.H., and D.D.H. are inventors on a patent 
      describing 10E8.2/iMab and 10E8.4/iMab. D.D.H. is the scientific founder of 
      TaiMed Biologics, Inc., which is focused on antibody therapies for HIV/AIDS.
EDAT- 2020/07/16 06:00
MHDA- 2020/09/18 06:00
PMCR- 2020/07/14
CRDT- 2020/07/16 06:00
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2020/07/16 06:00 [entrez]
PHST- 2020/07/14 00:00 [pmc-release]
AID - 2008190117 [pii]
AID - 202008190 [pii]
AID - 10.1073/pnas.2008190117 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):18002-18009. doi: 
      10.1073/pnas.2008190117. Epub 2020 Jul 14.