PMID- 31589165
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20240202
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 129
IP  - 11
DP  - 2019 Nov 1
TI  - Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.
PG  - 4838-4849
LID - 126391 [pii]
LID - 10.1172/JCI126391 [doi]
AB  - HVTN 505 is a preventative vaccine efficacy trial testing DNA followed by 
      recombinant adenovirus serotype 5 (rAd5) in circumcised, Ad5-seronegative men and 
      transgendered persons who have sex with men in the United States. Identified 
      immune correlates of lower HIV-1 risk and a virus sieve analysis revealed that, 
      despite lacking overall efficacy, vaccine-elicited responses exerted pressure on 
      infecting HIV-1 viruses. To interrogate the mechanism of the antibody correlate 
      of HIV-1 risk, we examined antigen-specific antibody recruitment of Fcgamma receptors 
      (FcgammaRs), antibody-dependent cellular phagocytosis (ADCP), and the role of 
      anti-envelope (anti-Env) IgG3. In a prespecified immune correlates analysis, 
      antibody-dependent monocyte phagocytosis and antibody binding to FcgammaRIIa 
      correlated with decreased HIV-1 risk. Follow-up analyses revealed that anti-Env 
      IgG3 breadth correlated with reduced HIV-1 risk, anti-Env IgA negatively modified 
      infection risk by Fc effector functions, and that vaccine recipients with a 
      specific FcgammaRIIa single-nucleotide polymorphism locus had a stronger correlation 
      with decreased HIV-1 risk when ADCP, Env-FcgammaRIIa, and IgG3 binding were high. 
      Additionally, FcgammaRIIa engagement correlated with decreased viral load setpoint in 
      vaccine recipients who acquired HIV-1. These data support a role for 
      vaccine-elicited anti-HIV-1 Env IgG3, antibody engagement of FcRs, and 
      phagocytosis as potential mechanisms for HIV-1 prevention.
FAU - Neidich, Scott D
AU  - Neidich SD
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Fong, Youyi
AU  - Fong Y
AD  - Statistical Center for HIV/AIDS Research and Prevention.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Biostatistics, University of Washington, Seattle, Washington, USA.
FAU - Li, Shuying S
AU  - Li SS
AD  - Statistical Center for HIV/AIDS Research and Prevention.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Geraghty, Daniel E
AU  - Geraghty DE
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
FAU - Williamson, Brian D
AU  - Williamson BD
AD  - Department of Biostatistics, University of Washington, Seattle, Washington, USA.
FAU - Young, William Chad
AU  - Young WC
AD  - Statistical Center for HIV/AIDS Research and Prevention.
FAU - Goodman, Derrick
AU  - Goodman D
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Seaton, Kelly E
AU  - Seaton KE
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Shen, Xiaoying
AU  - Shen X
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Sawant, Sheetal
AU  - Sawant S
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Zhang, Lu
AU  - Zhang L
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - deCamp, Allan C
AU  - deCamp AC
AD  - Statistical Center for HIV/AIDS Research and Prevention.
FAU - Blette, Bryan S
AU  - Blette BS
AD  - Department of Biostatistics, University of North Carolina Gillings School of 
      Global Public Health, Chapel Hill, North Carolina, USA.
FAU - Shao, Mengshu
AU  - Shao M
AD  - Statistical Center for HIV/AIDS Research and Prevention.
FAU - Yates, Nicole L
AU  - Yates NL
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Feely, Frederick
AU  - Feely F
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
FAU - Pyo, Chul-Woo
AU  - Pyo CW
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Ferrari, Guido
AU  - Ferrari G
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
AD  - Department of Surgery and.
AD  - Department of Molecular Genetics and Microbiology, Duke University, Durham, North 
      Carolina, USA.
CN  - HVTN 505 Team
FAU - Frank, Ian
AU  - Frank I
AD  - Division of Infectious Diseases, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia Pennsylvania, USA.
FAU - Karuna, Shelly T
AU  - Karuna ST
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Swann, Edith M
AU  - Swann EM
AD  - Division of AIDS and.
FAU - Mascola, John R
AU  - Mascola JR
AD  - Vaccine Research Center, National Institute of Allergy and Infectious Diseases 
      (NIAID), NIH, Bethesda, Maryland, USA.
FAU - Graham, Barney S
AU  - Graham BS
AD  - Vaccine Research Center, National Institute of Allergy and Infectious Diseases 
      (NIAID), NIH, Bethesda, Maryland, USA.
FAU - Hammer, Scott M
AU  - Hammer SM
AD  - Division of Infectious Diseases, Department of Medicine, Columbia University, New 
      York, New York, USA.
FAU - Sobieszczyk, Magdalena E
AU  - Sobieszczyk ME
AD  - Division of Infectious Diseases, Department of Medicine, Columbia University, New 
      York, New York, USA.
FAU - Corey, Lawrence
AU  - Corey L
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Janes, Holly E
AU  - Janes HE
AD  - Statistical Center for HIV/AIDS Research and Prevention.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Biostatistics, University of Washington, Seattle, Washington, USA.
FAU - McElrath, M Juliana
AU  - McElrath MJ
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Gottardo, Raphael
AU  - Gottardo R
AD  - Statistical Center for HIV/AIDS Research and Prevention.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Gilbert, Peter B
AU  - Gilbert PB
AD  - Statistical Center for HIV/AIDS Research and Prevention.
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Biostatistics, University of Washington, Seattle, Washington, USA.
FAU - Tomaras, Georgia D
AU  - Tomaras GD
AD  - Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
AD  - Department of Surgery and.
AD  - Department of Molecular Genetics and Microbiology, Duke University, Durham, North 
      Carolina, USA.
AD  - Department of Immunology, Duke University, Durham, North Carolina, USA.
LA  - eng
GR  - UM1 AI069534/AI/NIAID NIH HHS/United States
GR  - P30 AI045008/AI/NIAID NIH HHS/United States
GR  - R37 AI054165/AI/NIAID NIH HHS/United States
GR  - UM1 AI068635/AI/NIAID NIH HHS/United States
GR  - S10 OD020069/OD/NIH HHS/United States
GR  - P30 AI064518/AI/NIAID NIH HHS/United States
GR  - R01 AI122991/AI/NIAID NIH HHS/United States
GR  - UM1 AI068618/AI/NIAID NIH HHS/United States
GR  - P01 AI120756/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (AIDS Vaccines)
RN  - 0 (FCGR2A protein, human)
RN  - 0 (HIV Antibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
RN  - 0 (env Gene Products, Human Immunodeficiency Virus)
SB  - IM
CIN - J Clin Invest. 2019 Nov 1;129(11):4580-4582. PMID: 31589166
MH  - AIDS Vaccines/administration & dosage/*immunology
MH  - HIV Antibodies/*immunology
MH  - HIV Infections/genetics/*immunology/prevention & control
MH  - HIV-1/*immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, IgG/genetics/*immunology
MH  - Risk Factors
MH  - env Gene Products, Human Immunodeficiency Virus/immunology
PMC - PMC6819135
OTO - NOTNLM
OT  - AIDS vaccine
OT  - AIDS/HIV
OT  - Vaccines
COIS- Conflict of interest: PBG is the recipient of a contract from Sanofi Pasteur. GDT 
      is a recipient of a research subcontract from GSK. PBG has served as an unpaid 
      consultant at advisory meetings to Sanofi Pasteur and has received support for 
      travel to meetings from Sanofi Pasteur. GDT has patent applications for HIV 
      immunogens (nos. 14/130338, 201180021030.5, 13/262706, 15/195545, and 15/025,031) 
      and HIV incidence testing (16/315,688 HIV-1). SDN's spouse receives a salary from 
      Nuventra Pharma Sciences.
EDAT- 2019/10/08 06:00
MHDA- 2020/06/09 06:00
PMCR- 2020/02/01
CRDT- 2019/10/08 06:00
PHST- 2018/11/21 00:00 [received]
PHST- 2019/08/07 00:00 [accepted]
PHST- 2019/10/08 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/10/08 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - 126391 [pii]
AID - 10.1172/JCI126391 [doi]
PST - ppublish
SO  - J Clin Invest. 2019 Nov 1;129(11):4838-4849. doi: 10.1172/JCI126391.