PMID- 29712861
OWN - NLM
STAT- MEDLINE
DCOM- 20180828
LR  - 20180828
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 115
IP  - 24
DP  - 2018 Jun 12
TI  - HCMV glycoprotein B subunit vaccine efficacy mediated by nonneutralizing antibody
      effector functions.
PG  - 6267-6272
LID - 10.1073/pnas.1800177115 [doi]
AB  - Human cytomegalovirus (HCMV) is the most common congenital infection worldwide,
      frequently causing hearing loss and brain damage in afflicted infants. A vaccine 
      to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce
      the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit 
      vaccine platform is the most successful HCMV vaccine tested to date,
      demonstrating approximately 50% efficacy in preventing HCMV acquisition in
      multiple phase 2 trials. However, the mechanism of vaccine protection remains
      unknown. Plasma from 33 postpartum women gB/MF59 vaccinees at peak immunogenicity
      was tested for gB epitope specificity as well as neutralizing and nonneutralizing
      anti-HCMV effector functions and compared with an HCMV-seropositive cohort.
      gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity 
      comparable to natural infection. Additionally, IgG subclass distribution was
      similar with predominant IgG1 and IgG3 responses induced by gB vaccination and
      HCMV infection. However, vaccine-elicited antibodies exhibited limited
      neutralization of the autologous virus, negligible neutralization of multiple
      heterologous strains, and limited binding responses against gB structural motifs 
      targeted by neutralizing antibodies including AD-1, AD-2, and domain I. Vaccinees
      had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating
      immunodominance against this nonneutralizing, cytosolic region. Finally,
      vaccine-elicited IgG robustly bound membrane-associated gB on the surface of
      transfected or HCMV-infected cells and mediated virion phagocytosis, although
      were poor mediators of NK cell activation. Altogether, these data suggest that
      nonneutralizing antibody functions, including virion phagocytosis, likely played 
      a role in the observed 50% vaccine-mediated protection against HCMV acquisition.
FAU - Nelson, Cody S
AU  - Nelson CS
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
FAU - Huffman, Tori
AU  - Huffman T
AD  - Department of Surgery, Duke University Medical Center, Durham, NC 27710.
FAU - Jenks, Jennifer A
AU  - Jenks JA
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
FAU - Cisneros de la Rosa, Eduardo
AU  - Cisneros de la Rosa E
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
FAU - Xie, Guanhua
AU  - Xie G
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
FAU - Vandergrift, Nathan
AU  - Vandergrift N
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
FAU - Pass, Robert F
AU  - Pass RF
AD  - Department of Pediatrics, University of Alabama, Birmingham, AL 35233.
FAU - Pollara, Justin
AU  - Pollara J
AD  - Department of Surgery, Duke University Medical Center, Durham, NC 27710.
FAU - Permar, Sallie R
AU  - Permar SR
AD  - Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710;
      sallie.permar@duke.edu.
LA  - eng
GR  - DP2 HD075699/HD/NICHD NIH HHS/United States
GR  - F30 HD089577/HD/NICHD NIH HHS/United States
GR  - R21 AI136556/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20180430
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 (Antibodies, Viral)
RN  - 0 (Cytomegalovirus Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin G)
RN  - 0 (MF59 oil emulsion)
RN  - 0 (Polysorbates)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (glycoprotein B, Simplexvirus)
RN  - 7QWM220FJH (Squalene)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6110-6112. PMID: 29875141
MH  - Adult
MH  - Antibodies, Neutralizing/*immunology
MH  - Antibodies, Viral/immunology
MH  - Cells, Cultured
MH  - Cytomegalovirus/*immunology
MH  - Cytomegalovirus Infections/*immunology
MH  - Cytomegalovirus Vaccines/*immunology
MH  - Epitopes/immunology
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - Polysorbates
MH  - Squalene/immunology
MH  - Vaccines, Subunit/*immunology
MH  - Viral Envelope Proteins/*immunology
MH  - Young Adult
PMC - PMC6004431
OTO - NOTNLM
OT  - *cytomegalovirus
OT  - *glycoprotein B
OT  - *pediatrics
OT  - *vaccines
COIS- Conflict of interest statement: S.R.P. provides consulting services to Pfizer
      Inc. for their preclinical human cytomegalovirus vaccine program and associated
      animal models.
EDAT- 2018/05/02 06:00
MHDA- 2018/08/29 06:00
CRDT- 2018/05/02 06:00
PMCR- 2018/12/12 00:00
PHST- 2018/12/12 00:00 [pmc-release]
PHST- 2018/05/02 06:00 [pubmed]
PHST- 2018/08/29 06:00 [medline]
PHST- 2018/05/02 06:00 [entrez]
AID - 1800177115 [pii]
AID - 10.1073/pnas.1800177115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6267-6272. doi:
      10.1073/pnas.1800177115. Epub 2018 Apr 30.

PMID- 29731055
OWN - NLM
STAT- MEDLINE
DCOM- 20180828
LR  - 20180828
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 50
IP  - 4
DP  - 2018 May
TI  - Is the Clinical Outcome Good or Bad in Patients Hospitalized Within 1 Year After 
      Kidney Transplantation?
PG  - 1001-1004
LID - S0041-1345(18)30094-0 [pii]
LID - 10.1016/j.transproceed.2018.01.027 [doi]
AB  - BACKGROUND: Although the hospitalization rate at early period of kidney
      transplantation (KT) is still high, the association between the hospitalization
      within 1 year after KT and graft survival is unclear. We investigated the
      incidence and causes of hospitalization and clinical outcome of the patients
      hospitalized within 1 year after KT. METHODS: We retrospectively analyzed 174 KT 
      recipients (KTRs) hospitalized within 1 year after KT between 2013 and 2015.
      RESULTS: Among them, 84 (48%) KTRs were admitted within 1 year after KT, and the 
      number of hospitalizations was 116. The mean time from KT to first
      hospitalization was 4.2 months. Seventy-eight percent of the patients were
      hospitalized for medical causes and 22% for surgical causes. The most common
      cause was cytomegalovirus infection (CMV) (23.3%), followed by acute rejection
      (11.2%) and urinary tract infection (10.3%). Recipients and donors in the
      hospitalized group were significantly older than the nonhospitalized group. The
      proportions of deceased donor KT, acute rejection, more than 50% panel-reactive
      antibody, and positive donor-specific antibody were significantly higher in the
      hospitalized group than in the nonhospitalized group. Graft and patient survivals
      were lower in the hospitalized group than in the nonhospitalized group. Deceased 
      donor KT and acute rejection were independent risk factors for hospitalization.
      CONCLUSION: The incidence of KTRs hospitalized within 1 year after KT was high.
      Most causes of hospitalization were CMV infection, acute rejection, and urinary
      tract infection. Therefore, the immunosuppression status of these patients should
      be closely monitored to reduce the hospitalization rate.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Park, W Y
AU  - Park WY
AD  - Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
      Korea; Keimyung University Kidney Institute, Daegu, Korea.
FAU - Kang, S S
AU  - Kang SS
AD  - Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
      Korea; Keimyung University Kidney Institute, Daegu, Korea.
FAU - Jin, K
AU  - Jin K
AD  - Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
      Korea; Keimyung University Kidney Institute, Daegu, Korea.
FAU - Park, S B
AU  - Park SB
AD  - Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
      Korea; Keimyung University Kidney Institute, Daegu, Korea.
FAU - Han, S
AU  - Han S
AD  - Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
      Korea; Keimyung University Kidney Institute, Daegu, Korea. Electronic address:
      hansy@dsmc.or.kr.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
SB  - IM
MH  - Adult
MH  - Cytomegalovirus Infections/*epidemiology/immunology
MH  - Female
MH  - Graft Rejection/*epidemiology
MH  - Graft Survival
MH  - Hospitalization/statistics & numerical data
MH  - Humans
MH  - Immunocompromised Host
MH  - Immunosuppression/adverse effects
MH  - Incidence
MH  - Kaplan-Meier Estimate
MH  - Kidney Transplantation/*adverse effects/mortality
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Tissue Donors
EDAT- 2018/05/08 06:00
MHDA- 2018/08/29 06:00
CRDT- 2018/05/08 06:00
PHST- 2017/12/13 00:00 [received]
PHST- 2018/01/03 00:00 [accepted]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2018/08/29 06:00 [medline]
AID - S0041-1345(18)30094-0 [pii]
AID - 10.1016/j.transproceed.2018.01.027 [doi]
PST - ppublish
SO  - Transplant Proc. 2018 May;50(4):1001-1004. doi:
      10.1016/j.transproceed.2018.01.027.

PMID- 29631750
OWN - NLM
STAT- MEDLINE
DCOM- 20180828
LR  - 20180828
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 50
IP  - 4
DP  - 2018 May
TI  - Steroid Withdrawal Using Everolimus in ABO-Incompatible Kidney Transplant
      Recipients With Post-Transplant Diabetes Mellitus.
PG  - 1050-1055
LID - S0041-1345(18)30096-4 [pii]
LID - 10.1016/j.transproceed.2018.01.028 [doi]
AB  - BACKGROUND: The effectiveness of everolimus (EVR) for ABO-incompatible (ABOi)
      kidney transplantation is unknown. We evaluated outcomes of conversion from
      steroid to EVR in ABOi kidney transplant recipients. METHODS: We performed a
      retrospective observational cohort study of 33 de novo consecutive adult ABOi
      living donor kidney transplant recipients. Desensitization was performed using 0 
      to 4 sessions of plasmapheresis and 1 to 2 doses of 100 mg rituximab according to
      the anti-A/B antibody titer. ABOi recipients were administered a combination of
      tacrolimus, mycophenolate mofetil, and methylprednisolone. Diabetic patients were
      converted from methylprednisolone to EVR at 1 to 15 months post-transplantation
      to prevent diabetes progression. Graft outcomes, hemoglobin A1c (HbA1c) levels,
      and cytomegalovirus infection rates were compared between the EVR (n = 11) and
      steroid (n = 22) groups. RESULTS: Mean postoperative duration was 814 and 727
      days in the EVR and steroid groups, respectively (P = .65). Between the 2 groups,
      graft survival rate (100% vs 95.5%, P > .99), acute rejection rate (9.1% vs
      18.2%, P = .64), and serum creatinine levels (1.46 mg/dL vs 1.68 mg/dL, P = .66) 
      were comparable. Although HbA1c levels were elevated in the steroid group (5.47%,
      5.87%; P = .003), no significant deterioration was observed in the EVR group
      without additional insulin administration (6.10%, 6.47%; P = .21).
      Cytomegalovirus infection rate was significantly lower in the EVR group than in
      the steroid group (18.2% vs 63.6%, P = .026). CONCLUSION: Conversion from steroid
      to EVR in ABOi kidney transplant recipients maintained excellent graft outcomes
      and avoided diabetes progression and cytomegalovirus infection.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Nanmoku, K
AU  - Nanmoku K
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan. Electronic address: nan.nan.mock@gmail.com.
FAU - Shinzato, T
AU  - Shinzato T
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan.
FAU - Kubo, T
AU  - Kubo T
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan.
FAU - Shimizu, T
AU  - Shimizu T
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan.
FAU - Kimura, T
AU  - Kimura T
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan.
FAU - Yagisawa, T
AU  - Yagisawa T
AD  - Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital,
      Shimotsuke, Japan.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20180407
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Steroids)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 9HW64Q8G6G (Everolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Group Incompatibility
MH  - Cohort Studies
MH  - Cytomegalovirus Infections/epidemiology/etiology
MH  - *Diabetes Complications/epidemiology
MH  - *Diabetes Mellitus/drug therapy
MH  - *Drug Substitution/methods
MH  - Everolimus/*therapeutic use
MH  - Female
MH  - Graft Rejection/immunology
MH  - Graft Survival/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Incidence
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/therapeutic use
MH  - Plasmapheresis
MH  - Retrospective Studies
MH  - Rituximab/therapeutic use
MH  - Steroids/therapeutic use
MH  - Tacrolimus/therapeutic use
EDAT- 2018/04/11 06:00
MHDA- 2018/08/29 06:00
CRDT- 2018/04/11 06:00
PHST- 2017/12/09 00:00 [received]
PHST- 2018/01/06 00:00 [revised]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2018/08/29 06:00 [medline]
PHST- 2018/04/11 06:00 [entrez]
AID - S0041-1345(18)30096-4 [pii]
AID - 10.1016/j.transproceed.2018.01.028 [doi]
PST - ppublish
SO  - Transplant Proc. 2018 May;50(4):1050-1055. doi:
      10.1016/j.transproceed.2018.01.028. Epub 2018 Apr 7.

PMID- 30165311
OWN - NLM
STAT- MEDLINE
DCOM- 20181113
LR  - 20181113
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 524
DP  - 2018 Nov
TI  - Human cytomegalovirus-infected cells release extracellular vesicles that carry
      viral surface proteins.
PG  - 97-105
LID - S0042-6822(18)30249-6 [pii]
LID - 10.1016/j.virol.2018.08.008 [doi]
AB  - Extracellular vesicles (EVs) released by virus-infected cells typically
      incorporate host and viral components inside the vesicles (cargo molecules).
      Here, we investigated if human cytomegalovirus (HCMV) proteins are incorporated
      in EV outer membrane released by HCMV-infected cells. We separated EVs from HCMV 
      using an iodixanol step-gradient and found that the separated vesicles carried EV
      markers such as the tetraspanin CD63 and Rab27A. Flow analysis of individual EVs 
      demonstrated that on average, 15+/-3.7% of EVs were positive for gB, 5.3+/-2.3%
      were positive for gH and 3.74+/-1.5% were positive for both gB and gH. In light
      of previous findings demonstrating HIV envelope proteins in EV membranes, the
      presence of viral protein at the surface of EVs released by HCMV-infected cells
      indicated that viral membrane proteins incorporated in EVs released by
      virus-infected cells may be a general phenomenon.
CI  - Published by Elsevier Inc.
FAU - Zicari, Sonia
AU  - Zicari S
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States.
FAU - Arakelyan, Anush
AU  - Arakelyan A
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States.
FAU - Palomino, Rogers Alberto Nahui
AU  - Palomino RAN
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States.
FAU - Fitzgerald, Wendy
AU  - Fitzgerald W
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States.
FAU - Vanpouille, Christophe
AU  - Vanpouille C
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States.
FAU - Lebedeva, Anna
AU  - Lebedeva A
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States; Evdokimov University of Medicine and Dentistry, Moscow,
      Russia.
FAU - Schmitt, Alain
AU  - Schmitt A
AD  - EM Facility, Paris, France; U1016INSERM, Paris, France; UMR 8104 CNRS, Paris,
      France.
FAU - Bomsel, Morgane
AU  - Bomsel M
AD  - U1016INSERM, Paris, France; UMR 8104 CNRS, Paris, France; Mucosal entry of HIV
      and mucosal immunity, Cochin Institute, Paris Descartes University, Paris,
      France.
FAU - Britt, William
AU  - Britt W
AD  - Departments of Pediatrics, Microbiology, and Neurobiology, University of Alabama 
      School of Medicine, Birmingham, AL, United States.
FAU - Margolis, Leonid
AU  - Margolis L
AD  - Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute
      of Child Health and Human Development, National Institutes of Health, Bethesda,
      MD, United States. Electronic address: margolil@helix.nih.gov.
LA  - eng
GR  - R01 AI089956/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180827
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Biomarkers)
RN  - 0 (CD63 protein, human)
RN  - 0 (Tetraspanin 30)
RN  - 0 (Triiodobenzoic Acids)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (rab27 GTP-Binding Proteins)
RN  - EC 3.6.1.-. (RAB27A protein, human)
RN  - HW8W27HTXX (iodixanol)
SB  - IM
MH  - Biomarkers/analysis
MH  - Cytomegalovirus/*metabolism
MH  - Cytomegalovirus Infections/*virology
MH  - Extracellular Vesicles/*metabolism/virology
MH  - Genes, Reporter
MH  - Humans
MH  - Protein Transport
MH  - Tetraspanin 30/*analysis
MH  - Triiodobenzoic Acids
MH  - Viral Matrix Proteins/*metabolism
MH  - Virion
MH  - rab27 GTP-Binding Proteins/*analysis
OTO - NOTNLM
OT  - *Extracellular vesicles
OT  - *HCMV
OT  - *gB
OT  - *gH
EDAT- 2018/08/31 06:00
MHDA- 2018/11/14 06:00
CRDT- 2018/08/31 06:00
PHST- 2018/04/13 00:00 [received]
PHST- 2018/08/08 00:00 [revised]
PHST- 2018/08/08 00:00 [accepted]
PHST- 2018/08/31 06:00 [pubmed]
PHST- 2018/11/14 06:00 [medline]
PHST- 2018/08/31 06:00 [entrez]
AID - S0042-6822(18)30249-6 [pii]
AID - 10.1016/j.virol.2018.08.008 [doi]
PST - ppublish
SO  - Virology. 2018 Nov;524:97-105. doi: 10.1016/j.virol.2018.08.008. Epub 2018 Aug
      27.