PMID- 28701403
OWN - NLM
STAT- MEDLINE
DCOM- 20170926
LR  - 20180403
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 19
DP  - 2017 Oct 1
TI  - Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine 
      Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, 
      Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and
      Protect Mice from Ocular Challenge with HSV-1.
LID - e00411-17 [pii]
LID - 10.1128/JVI.00411-17 [doi]
AB  - The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120)
      construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein
      D (gD) so that the first 40 amino acids of gp120 were replaced by the signal
      sequence and the first 27 amino acids of the mature form of gD. This region of gD
      contains most of the binding site for HVEM, an HSV receptor important for virus
      infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV
      that were partially protective against infection, as well as antibodies to HSV.
      We derived monoclonal antibodies (MAbs) from peripheral blood B cells of
      recipients of the RV144 HIV vaccine and showed that these antibodies neutralized 
      HSV-1 infection in cells expressing HVEM, but not the other major virus receptor,
      nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and 
      mice that received the MAbs and were then challenged by corneal inoculation with 
      HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, 
      this is the first description of MAbs derived from human recipients of a vaccine 
      that specifically target the HVEM binding site of gD. In summary, we found that
      monoclonal antibodies derived from humans vaccinated with the HVEM binding domain
      of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner,
      (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected
      mice.IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal
      herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine
      has been approved. Nectin-1 and HVEM are the two major cellular receptors for
      HSV. These receptors are expressed at different levels in various tissues, and
      the role of each receptor in HSV pathogenesis is not well understood. We derived 
      human monoclonal antibodies from persons who received the HIV RV144 vaccine that 
      contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These
      antibodies were able to specifically neutralize HSV-1 infection in vitro via
      HVEM. Furthermore, we showed for the first time that HVEM-specific HSV-1
      neutralizing antibodies protect mice from HSV-1 eye disease, indicating the
      critical role of HVEM in HSV-1 ocular infection.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Wang, Kening
AU  - Wang K
AD  - Medical Virology Section, Laboratory of Infectious Diseases, National Institute
      of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,
      Maryland, USA.
FAU - Tomaras, Georgia D
AU  - Tomaras GD
AD  - Departments of Surgery, Immunology, and Molecular Genetics and Microbiology, Duke
      Human Vaccine Institute, Duke University School of Medicine, Durham, North
      Carolina, USA.
FAU - Jegaskanda, Sinthujan
AU  - Jegaskanda S
AD  - Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National
      Institute of Allergy and Infectious Diseases, National Institutes of Health,
      Bethesda, Maryland, USA.
FAU - Moody, M Anthony
AU  - Moody MA
AD  - Departments of Pediatrics and Immunology, Duke Human Vaccine Institute, Duke
      University School of Medicine, Durham, North Carolina, USA.
FAU - Liao, Hua-Xin
AU  - Liao HX
AD  - Departments of Surgery, Immunology, and Molecular Genetics and Microbiology, Duke
      Human Vaccine Institute, Duke University School of Medicine, Durham, North
      Carolina, USA.
FAU - Goodman, Kyle N
AU  - Goodman KN
AD  - Medical Virology Section, Laboratory of Infectious Diseases, National Institute
      of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,
      Maryland, USA.
FAU - Berman, Phillip W
AU  - Berman PW
AD  - Department of Biomolecular Engineering, University of California, Santa Cruz,
      California, USA.
FAU - Rerks-Ngarm, Supachai
AU  - Rerks-Ngarm S
AD  - Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
FAU - Pitisuttithum, Punnee
AU  - Pitisuttithum P
AD  - Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
FAU - Nitayapan, Sorachai
AU  - Nitayapan S
AD  - Royal Thai Army, Armed Forces Research Institute of Medical Sciences (AFRIMS),
      Bangkok, Thailand.
FAU - Kaewkungwal, Jaranit
AU  - Kaewkungwal J
AD  - Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
FAU - Haynes, Barton F
AU  - Haynes BF
AD  - Departments of Medicine and Immunology, Duke Human Vaccine Institute, Duke
      University School of Medicine, Durham, North Carolina, USA.
FAU - Cohen, Jeffrey I
AU  - Cohen JI
AD  - Medical Virology Section, Laboratory of Infectious Diseases, National Institute
      of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,
      Maryland, USA jcohen@niaid.nih.gov.
LA  - eng
GR  - P30 AI064518/AI/NIAID NIH HHS/United States
GR  - K23 AI067501/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, N.I.H., Extramural
DEP - 20170912
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (AIDS Vaccines)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 14)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (glycoprotein D, Human herpesvirus 1)
RN  - 0 (gp120 protein, Human immunodeficiency virus 1)
SB  - IM
MH  - AIDS Vaccines/*immunology
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage/*immunology
MH  - Antibody-Dependent Cell Cytotoxicity/immunology
MH  - Cell Line
MH  - Eye Diseases/*prevention & control/virology
MH  - Female
MH  - HIV Envelope Protein gp120/genetics/*immunology
MH  - Herpes Simplex/immunology/*prevention & control/virology
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Leukocytes, Mononuclear/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, Tumor Necrosis Factor, Member 14/*immunology
MH  - Simplexvirus/genetics/*immunology
MH  - Viral Envelope Proteins/genetics/*immunology
PMC - PMC5599770
OTO - NOTNLM
OT  - *ADCC
OT  - *HIV vaccine
OT  - *HVEM
OT  - *glycoprotein D
OT  - *herpes simplex virus
OT  - *monoclonal antibody
OT  - *ocular infection
EDAT- 2017/07/14 06:00
MHDA- 2017/09/28 06:00
CRDT- 2017/07/14 06:00
PHST- 2017/03/14 00:00 [received]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/07/14 06:00 [pubmed]
PHST- 2017/09/28 06:00 [medline]
PHST- 2017/07/14 06:00 [entrez]
AID - JVI.00411-17 [pii]
AID - 10.1128/JVI.00411-17 [doi]
PST - epublish
SO  - J Virol. 2017 Sep 12;91(19). pii: JVI.00411-17. doi: 10.1128/JVI.00411-17. Print 
      2017 Oct 1.