schliessen

Filtern

 

Bibliotheken

Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial

Summary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vac... Full description

Journal Title: Lancet 2011, Vol.377 (9773), p.1256-1263
Main Author: Griffiths, Paul D, Prof
Other Authors: Stanton, Anna, RN , McCarrell, Erin, MSc , Smith, Colette, PhD , Osman, Mohamed, PhD , Harber, Mark, FRCP , Davenport, Andrew, FRCP , Jones, Gareth, MRCP , Wheeler, David C, FRCP , O'Beirne, James, MRCP , Thorburn, Douglas, FRCP , Patch, David, FRCP , Atkinson, Claire E, MSc , Pichon, Sylvie, MSc , Sweny, Paul, FRCP , Lanzman, Marisa, MRPharmS , Woodford, Elizabeth , Rothwell, Emily, RGN , Old, Natasha, BA , Kinyanjui, Ruth, RN , Haque, Tanzina, FRCPath , Atabani, Sowsan, MRCPath , Luck, Suzanne, MBChB , Prideaux, Steven, BSc , Milne, Richard SB, PhD , Emery, Vincent C, Prof , Burroughs, Andrew K, Prof
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3075549
title: Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
format: Article
creator:
  • Griffiths, Paul D, Prof
  • Stanton, Anna, RN
  • McCarrell, Erin, MSc
  • Smith, Colette, PhD
  • Osman, Mohamed, PhD
  • Harber, Mark, FRCP
  • Davenport, Andrew, FRCP
  • Jones, Gareth, MRCP
  • Wheeler, David C, FRCP
  • O'Beirne, James, MRCP
  • Thorburn, Douglas, FRCP
  • Patch, David, FRCP
  • Atkinson, Claire E, MSc
  • Pichon, Sylvie, MSc
  • Sweny, Paul, FRCP
  • Lanzman, Marisa, MRPharmS
  • Woodford, Elizabeth
  • Rothwell, Emily, RGN
  • Old, Natasha, BA
  • Kinyanjui, Ruth, RN
  • Haque, Tanzina, FRCPath
  • Atabani, Sowsan, MRCPath
  • Luck, Suzanne, MBChB
  • Prideaux, Steven, BSc
  • Milne, Richard SB, PhD
  • Emery, Vincent C, Prof
  • Burroughs, Andrew K, Prof
subjects:
  • Adjuvants
  • Adjuvants, Immunologic - administration & dosage
  • Adult
  • Aged
  • Albumin
  • Antibodies
  • Antibodies, Viral - isolation & purification
  • Articles
  • Biological and medical sciences
  • Blood products
  • Clinical trials
  • Cytomegalovirus
  • Cytomegalovirus - genetics
  • Cytomegalovirus - immunology
  • Cytomegalovirus - isolation & purification
  • Cytomegalovirus Infections - diagnosis
  • Cytomegalovirus Infections - prevention & control
  • Cytomegalovirus Vaccines - administration & dosage
  • Cytomegalovirus Vaccines - pharmacology
  • Cytomegaloviruses
  • Design
  • Disease
  • DNA, Viral - isolation & purification
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ganciclovir
  • General aspects
  • Genomes
  • glycoprotein B
  • Health aspects
  • Hospitals
  • Humans
  • Hypersensitivity
  • Immunity
  • Immunity (cell-mediated)
  • Immunity (humoral)
  • Immunogenicity
  • Immunosuppressive Agents - administration & dosage
  • Immunosuppressive Agents - adverse effects
  • Infectious diseases
  • Internal Medicine
  • Kidney Transplantation
  • Liver Transplantation
  • Male
  • Medical sciences
  • Middle Aged
  • Motivation
  • Organ transplant recipients
  • Organ Transplantation
  • Polymerase Chain Reaction
  • Polysorbates - administration & dosage
  • Pregnancy
  • Squalene - administration & dosage
  • Time Factors
  • Treatment Outcome
  • Usage
  • Vaccines
  • Viral diseases
  • Viral Envelope Proteins - administration & dosage
  • Viral Envelope Proteins - pharmacology
  • Viral vaccines
  • Viremia
  • Viremia - diagnosis
  • Viremia - prevention & control
  • virus diseases
ispartof: Lancet, 2011, Vol.377 (9773), p.1256-1263
description: Summary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov , NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.7299876
LOCALfalse
PrimoNMBib
record
control
sourceidgale_pubme
recordidTN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3075549
sourceformatXML
sourcesystemPC
galeidA253759443
sourcerecordidA253759443
originalsourceidFETCH-LOGICAL-1780t-e7c968198508b112b3b5cc35653800dcb37d5d177d7aab03b70db775762b86993
addsrcrecordideNqFkl-L1DAUxYso7rr6EZSiiAp2TZomaRVW1sV1hRUfVPAt5M-dmYydpibpyDz6zU13xnFnEJZCS5PfPZx778myhxgdY4TZqy8IV6hgnLDnGL9gCBNWoFvZIa54VdCKf7-dHW6Rg-xeCHOEUMUQvZsdlLiqMUf1Yfb7bBXdAqaydUvrh5BP25V2vXcRbFe8y5dSa9tB_svGWf7pnDa5NPNhKbuY2y6PXnahb8c_D9r2FroYXucy72cyQF7m6d64hQ1g8oRpUK7QrovetW06it7K9n52ZyLbAA8236Ps2_n7r2cXxeXnDx_PTi8LzGsUC-C6YTVuaopqhXGpiKJaE8ooqREyWhFuqMGcGy6lQkRxZBTnlLNS1axpyFF2stbtB7UAo5NVL1vRe7uQfiWctGL3prMzMXVLQRCntBoFLtYCrodOWg87taaDKJwRJeNiUtXUKAWact6UBJipAZUclURh2pQsST3bePHu5wAhijQjDW2aJLghiCahFeMcJfLxHjl3g-_SoETNMCtTh6PckzWU1gjCdhOXGtCjpDgtKeG0qSqSqOP_UOkxsLBpKzCx6Xyn4OW1AjWEFISQXsFOZzFM5RDCLk7XuPYuBA-T7XwwEmNmxVVmxRhIgbG4yqwYW3x0fTHbqr8hTcDTDSCDlu0khUrb8I-rUFUyNhp4s2dA2yijHQMnbXujjbfrakghXFrwIuiUZw0mrVpHYZy9UeFkT0G3trPJ8g9YQdguDotQCrQWGTUwvlJA5A9epS33
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid861627756
display
typearticle
titleCytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
sourceAlma/SFX Local Collection
creatorGriffiths, Paul D, Prof ; Stanton, Anna, RN ; McCarrell, Erin, MSc ; Smith, Colette, PhD ; Osman, Mohamed, PhD ; Harber, Mark, FRCP ; Davenport, Andrew, FRCP ; Jones, Gareth, MRCP ; Wheeler, David C, FRCP ; O'Beirne, James, MRCP ; Thorburn, Douglas, FRCP ; Patch, David, FRCP ; Atkinson, Claire E, MSc ; Pichon, Sylvie, MSc ; Sweny, Paul, FRCP ; Lanzman, Marisa, MRPharmS ; Woodford, Elizabeth ; Rothwell, Emily, RGN ; Old, Natasha, BA ; Kinyanjui, Ruth, RN ; Haque, Tanzina, FRCPath ; Atabani, Sowsan, MRCPath ; Luck, Suzanne, MBChB ; Prideaux, Steven, BSc ; Milne, Richard SB, PhD ; Emery, Vincent C, Prof ; Burroughs, Andrew K, Prof
creatorcontribGriffiths, Paul D, Prof ; Stanton, Anna, RN ; McCarrell, Erin, MSc ; Smith, Colette, PhD ; Osman, Mohamed, PhD ; Harber, Mark, FRCP ; Davenport, Andrew, FRCP ; Jones, Gareth, MRCP ; Wheeler, David C, FRCP ; O'Beirne, James, MRCP ; Thorburn, Douglas, FRCP ; Patch, David, FRCP ; Atkinson, Claire E, MSc ; Pichon, Sylvie, MSc ; Sweny, Paul, FRCP ; Lanzman, Marisa, MRPharmS ; Woodford, Elizabeth ; Rothwell, Emily, RGN ; Old, Natasha, BA ; Kinyanjui, Ruth, RN ; Haque, Tanzina, FRCPath ; Atabani, Sowsan, MRCPath ; Luck, Suzanne, MBChB ; Prideaux, Steven, BSc ; Milne, Richard SB, PhD ; Emery, Vincent C, Prof ; Burroughs, Andrew K, Prof
descriptionSummary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov , NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Interpretation Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. Funding National Institute of Allergy and Infectious Diseases , Grant R01AI051355 and Wellcome Trust , Grant 078332 . Sponsor: University College London (UCL).
identifier
0ISSN: 0140-6736
1EISSN: 1474-547X
2DOI: 10.1016/S0140-6736(11)60136-0
3PMID: 21481708
4CODEN: LANCAO
languageeng
publisherKidlington: Elsevier Ltd
subject
ispartofLancet, 2011, Vol.377 (9773), p.1256-1263
rights
0Elsevier Ltd
12011 Elsevier Ltd
22015 INIST-CNRS
3Copyright © 2011 Elsevier Ltd. All rights reserved.
4COPYRIGHT 2011 Elsevier B.V.
5Copyright Elsevier Limited Apr 9-Apr 15, 2011
62011 Elsevier Ltd. All rights reserved. 2011 Elsevier Ltd
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1780t-e7c968198508b112b3b5cc35653800dcb37d5d177d7aab03b70db775762b86993
citesFETCH-LOGICAL-1780t-e7c968198508b112b3b5cc35653800dcb37d5d177d7aab03b70db775762b86993
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24042663$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21481708$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Griffiths, Paul D, Prof
1Stanton, Anna, RN
2McCarrell, Erin, MSc
3Smith, Colette, PhD
4Osman, Mohamed, PhD
5Harber, Mark, FRCP
6Davenport, Andrew, FRCP
7Jones, Gareth, MRCP
8Wheeler, David C, FRCP
9O'Beirne, James, MRCP
10Thorburn, Douglas, FRCP
11Patch, David, FRCP
12Atkinson, Claire E, MSc
13Pichon, Sylvie, MSc
14Sweny, Paul, FRCP
15Lanzman, Marisa, MRPharmS
16Woodford, Elizabeth
17Rothwell, Emily, RGN
18Old, Natasha, BA
19Kinyanjui, Ruth, RN
20Haque, Tanzina, FRCPath
21Atabani, Sowsan, MRCPath
22Luck, Suzanne, MBChB
23Prideaux, Steven, BSc
24Milne, Richard SB, PhD
25Emery, Vincent C, Prof
26Burroughs, Andrew K, Prof
title
0Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
1Lancet
addtitleLancet
descriptionSummary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov , NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Interpretation Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. Funding National Institute of Allergy and Infectious Diseases , Grant R01AI051355 and Wellcome Trust , Grant 078332 . Sponsor: University College London (UCL).
subject
0Adjuvants
1Adjuvants, Immunologic - administration & dosage
2Adult
3Aged
4Albumin
5Antibodies
6Antibodies, Viral - isolation & purification
7Articles
8Biological and medical sciences
9Blood products
10Clinical trials
11Cytomegalovirus
12Cytomegalovirus - genetics
13Cytomegalovirus - immunology
14Cytomegalovirus - isolation & purification
15Cytomegalovirus Infections - diagnosis
16Cytomegalovirus Infections - prevention & control
17Cytomegalovirus Vaccines - administration & dosage
18Cytomegalovirus Vaccines - pharmacology
19Cytomegaloviruses
20Design
21Disease
22DNA, Viral - isolation & purification
23Enzyme-Linked Immunosorbent Assay
24Female
25Ganciclovir
26General aspects
27Genomes
28glycoprotein B
29Health aspects
30Hospitals
31Humans
32Hypersensitivity
33Immunity
34Immunity (cell-mediated)
35Immunity (humoral)
36Immunogenicity
37Immunosuppressive Agents - administration & dosage
38Immunosuppressive Agents - adverse effects
39Infectious diseases
40Internal Medicine
41Kidney Transplantation
42Liver Transplantation
43Male
44Medical sciences
45Middle Aged
46Motivation
47Organ transplant recipients
48Organ Transplantation
49Polymerase Chain Reaction
50Polysorbates - administration & dosage
51Pregnancy
52Squalene - administration & dosage
53Time Factors
54Treatment Outcome
55Usage
56Vaccines
57Viral diseases
58Viral Envelope Proteins - administration & dosage
59Viral Envelope Proteins - pharmacology
60Viral vaccines
61Viremia
62Viremia - diagnosis
63Viremia - prevention & control
64virus diseases
issn
00140-6736
11474-547X
fulltexttrue
rsrctypearticle
creationdate2011
recordtypearticle
recordideNqFkl-L1DAUxYso7rr6EZSiiAp2TZomaRVW1sV1hRUfVPAt5M-dmYydpibpyDz6zU13xnFnEJZCS5PfPZx778myhxgdY4TZqy8IV6hgnLDnGL9gCBNWoFvZIa54VdCKf7-dHW6Rg-xeCHOEUMUQvZsdlLiqMUf1Yfb7bBXdAqaydUvrh5BP25V2vXcRbFe8y5dSa9tB_svGWf7pnDa5NPNhKbuY2y6PXnahb8c_D9r2FroYXucy72cyQF7m6d64hQ1g8oRpUK7QrovetW06it7K9n52ZyLbAA8236Ps2_n7r2cXxeXnDx_PTi8LzGsUC-C6YTVuaopqhXGpiKJaE8ooqREyWhFuqMGcGy6lQkRxZBTnlLNS1axpyFF2stbtB7UAo5NVL1vRe7uQfiWctGL3prMzMXVLQRCntBoFLtYCrodOWg87taaDKJwRJeNiUtXUKAWact6UBJipAZUclURh2pQsST3bePHu5wAhijQjDW2aJLghiCahFeMcJfLxHjl3g-_SoETNMCtTh6PckzWU1gjCdhOXGtCjpDgtKeG0qSqSqOP_UOkxsLBpKzCx6Xyn4OW1AjWEFISQXsFOZzFM5RDCLk7XuPYuBA-T7XwwEmNmxVVmxRhIgbG4yqwYW3x0fTHbqr8hTcDTDSCDlu0khUrb8I-rUFUyNhp4s2dA2yijHQMnbXujjbfrakghXFrwIuiUZw0mrVpHYZy9UeFkT0G3trPJ8g9YQdguDotQCrQWGTUwvlJA5A9epS33
startdate2011
enddate2011
creator
0Griffiths, Paul D, Prof
1Stanton, Anna, RN
2McCarrell, Erin, MSc
3Smith, Colette, PhD
4Osman, Mohamed, PhD
5Harber, Mark, FRCP
6Davenport, Andrew, FRCP
7Jones, Gareth, MRCP
8Wheeler, David C, FRCP
9O'Beirne, James, MRCP
10Thorburn, Douglas, FRCP
11Patch, David, FRCP
12Atkinson, Claire E, MSc
13Pichon, Sylvie, MSc
14Sweny, Paul, FRCP
15Lanzman, Marisa, MRPharmS
16Woodford, Elizabeth
17Rothwell, Emily, RGN
18Old, Natasha, BA
19Kinyanjui, Ruth, RN
20Haque, Tanzina, FRCPath
21Atabani, Sowsan, MRCPath
22Luck, Suzanne, MBChB
23Prideaux, Steven, BSc
24Milne, Richard SB, PhD
25Emery, Vincent C, Prof
26Burroughs, Andrew K, Prof
general
0Elsevier Ltd
1Elsevier
2Elsevier B.V
3Elsevier Limited
4Lancet Publishing Group
scope
06I.
1AAFTH
2IQODW
3CGR
4CUY
5CVF
6ECM
7EIF
8NPM
9AAYXX
10CITATION
11BSHEE
120TT
130TZ
140U~
153V.
167QL
177QP
187RV
197TK
207U7
217U9
227X7
237XB
2488A
2588C
2688E
2788G
2888I
298AF
308AO
318C1
328C2
338FE
348FH
358FI
368FJ
378FK
388G5
39ABUWG
40AN0
41ASE
42AZQEC
43BBNVY
44BEC
45BENPR
46BHPHI
47C1K
48DWQXO
49FPQ
50FYUFA
51GHDGH
52GNUQQ
53GUQSH
54H94
55HCIFZ
56K6X
57K9-
58K9.
59KB0
60KB~
61LK8
62M0R
63M0S
64M0T
65M1P
66M2M
67M2O
68M2P
69M7N
70M7P
71MBDVC
72NAPCQ
73PQEST
74PQQKQ
75PQUKI
76Q9U
77S0X
78BOBZL
79CLFQK
805PM
sort
creationdate2011
titleCytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
authorGriffiths, Paul D, Prof ; Stanton, Anna, RN ; McCarrell, Erin, MSc ; Smith, Colette, PhD ; Osman, Mohamed, PhD ; Harber, Mark, FRCP ; Davenport, Andrew, FRCP ; Jones, Gareth, MRCP ; Wheeler, David C, FRCP ; O'Beirne, James, MRCP ; Thorburn, Douglas, FRCP ; Patch, David, FRCP ; Atkinson, Claire E, MSc ; Pichon, Sylvie, MSc ; Sweny, Paul, FRCP ; Lanzman, Marisa, MRPharmS ; Woodford, Elizabeth ; Rothwell, Emily, RGN ; Old, Natasha, BA ; Kinyanjui, Ruth, RN ; Haque, Tanzina, FRCPath ; Atabani, Sowsan, MRCPath ; Luck, Suzanne, MBChB ; Prideaux, Steven, BSc ; Milne, Richard SB, PhD ; Emery, Vincent C, Prof ; Burroughs, Andrew K, Prof
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1780t-e7c968198508b112b3b5cc35653800dcb37d5d177d7aab03b70db775762b86993
rsrctypearticles
prefilterarticles
languageeng
creationdate2011
topic
0Adjuvants
1Adjuvants, Immunologic - administration & dosage
2Adult
3Aged
4Albumin
5Antibodies
6Antibodies, Viral - isolation & purification
7Articles
8Biological and medical sciences
9Blood products
10Clinical trials
11Cytomegalovirus
12Cytomegalovirus - genetics
13Cytomegalovirus - immunology
14Cytomegalovirus - isolation & purification
15Cytomegalovirus Infections - diagnosis
16Cytomegalovirus Infections - prevention & control
17Cytomegalovirus Vaccines - administration & dosage
18Cytomegalovirus Vaccines - pharmacology
19Cytomegaloviruses
20Design
21Disease
22DNA, Viral - isolation & purification
23Enzyme-Linked Immunosorbent Assay
24Female
25Ganciclovir
26General aspects
27Genomes
28glycoprotein B
29Health aspects
30Hospitals
31Humans
32Hypersensitivity
33Immunity
34Immunity (cell-mediated)
35Immunity (humoral)
36Immunogenicity
37Immunosuppressive Agents - administration & dosage
38Immunosuppressive Agents - adverse effects
39Infectious diseases
40Internal Medicine
41Kidney Transplantation
42Liver Transplantation
43Male
44Medical sciences
45Middle Aged
46Motivation
47Organ transplant recipients
48Organ Transplantation
49Polymerase Chain Reaction
50Polysorbates - administration & dosage
51Pregnancy
52Squalene - administration & dosage
53Time Factors
54Treatment Outcome
55Usage
56Vaccines
57Viral diseases
58Viral Envelope Proteins - administration & dosage
59Viral Envelope Proteins - pharmacology
60Viral vaccines
61Viremia
62Viremia - diagnosis
63Viremia - prevention & control
64virus diseases
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Griffiths, Paul D, Prof
1Stanton, Anna, RN
2McCarrell, Erin, MSc
3Smith, Colette, PhD
4Osman, Mohamed, PhD
5Harber, Mark, FRCP
6Davenport, Andrew, FRCP
7Jones, Gareth, MRCP
8Wheeler, David C, FRCP
9O'Beirne, James, MRCP
10Thorburn, Douglas, FRCP
11Patch, David, FRCP
12Atkinson, Claire E, MSc
13Pichon, Sylvie, MSc
14Sweny, Paul, FRCP
15Lanzman, Marisa, MRPharmS
16Woodford, Elizabeth
17Rothwell, Emily, RGN
18Old, Natasha, BA
19Kinyanjui, Ruth, RN
20Haque, Tanzina, FRCPath
21Atabani, Sowsan, MRCPath
22Luck, Suzanne, MBChB
23Prideaux, Steven, BSc
24Milne, Richard SB, PhD
25Emery, Vincent C, Prof
26Burroughs, Andrew K, Prof
collection
0ScienceDirect Open Access Titles
1Elsevier:ScienceDirect:Open Access
2Pascal-Francis
3Medline
4MEDLINE
5MEDLINE (Ovid)
6MEDLINE
7MEDLINE
8PubMed
9CrossRef
10Academic OneFile (A&I only)
11News PRO
12Pharma and Biotech Premium PRO
13Global News & ABI/Inform Professional
14ProQuest Central (Corporate)
15Bacteriology Abstracts (Microbiology B)
16Calcium & Calcified Tissue Abstracts
17Nursing & Allied Health Database
18Neurosciences Abstracts
19Toxicology Abstracts
20Virology and AIDS Abstracts
21Health & Medical Collection
22ProQuest Central (purchase pre-March 2016)
23Biology Database (Alumni Edition)
24Healthcare Administration Database (Alumni)
25Medical Database (Alumni Edition)
26Psychology Database (Alumni)
27Science Database (Alumni Edition)
28STEM Database
29ProQuest Pharma Collection
30Public Health Database
31Lancet Titles
32ProQuest SciTech Collection
33ProQuest Natural Science Collection
34Hospital Premium Collection
35Hospital Premium Collection (Alumni Edition)
36ProQuest Central (Alumni) (purchase pre-March 2016)
37Research Library (Alumni Edition)
38ProQuest Central (Alumni Edition)
39British Nursing Database
40British Nursing Index
41ProQuest Central Essentials
42Biological Science Collection
43eLibrary
44ProQuest Central
45Natural Science Collection
46Environmental Sciences and Pollution Management
47ProQuest Central Korea
48British Nursing Index (BNI) (1985 to Present)
49Health Research Premium Collection
50Health Research Premium Collection (Alumni)
51ProQuest Central Student
52Research Library Prep
53AIDS and Cancer Research Abstracts
54SciTech Premium Collection
55British Nursing Index
56Consumer Health Database (Alumni Edition)
57ProQuest Health & Medical Complete (Alumni)
58Nursing & Allied Health Database (Alumni Edition)
59ProQuest Newsstand Professional
60ProQuest Biological Science Collection
61Consumer Health Database
62Health & Medical Collection (Alumni Edition)
63Healthcare Administration Database
64Medical Database
65Psychology Database
66Research Library
67Science Database
68Algology Mycology and Protozoology Abstracts (Microbiology C)
69Biological Science Database
70Research Library (Corporate)
71Nursing & Allied Health Premium
72ProQuest One Academic Eastern Edition
73ProQuest One Academic
74ProQuest One Academic UKI Edition
75ProQuest Central Basic
76SIRS Editorial
77OpenAIRE (Open Access)
78OpenAIRE
79PubMed Central (Full Participant titles)
jtitleLancet
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Griffiths, Paul D, Prof
1Stanton, Anna, RN
2McCarrell, Erin, MSc
3Smith, Colette, PhD
4Osman, Mohamed, PhD
5Harber, Mark, FRCP
6Davenport, Andrew, FRCP
7Jones, Gareth, MRCP
8Wheeler, David C, FRCP
9O'Beirne, James, MRCP
10Thorburn, Douglas, FRCP
11Patch, David, FRCP
12Atkinson, Claire E, MSc
13Pichon, Sylvie, MSc
14Sweny, Paul, FRCP
15Lanzman, Marisa, MRPharmS
16Woodford, Elizabeth
17Rothwell, Emily, RGN
18Old, Natasha, BA
19Kinyanjui, Ruth, RN
20Haque, Tanzina, FRCPath
21Atabani, Sowsan, MRCPath
22Luck, Suzanne, MBChB
23Prideaux, Steven, BSc
24Milne, Richard SB, PhD
25Emery, Vincent C, Prof
26Burroughs, Andrew K, Prof
formatjournal
genrearticle
ristypeJOUR
atitleCytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
jtitleLancet
addtitleLancet
date2011
risdate2011
volume377
issue9773
spage1256
epage1263
pages1256-1263
issn0140-6736
eissn1474-547X
codenLANCAO
abstractSummary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov , NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Interpretation Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. Funding National Institute of Allergy and Infectious Diseases , Grant R01AI051355 and Wellcome Trust , Grant 078332 . Sponsor: University College London (UCL).
copKidlington
pubElsevier Ltd
pmid21481708
doi10.1016/S0140-6736(11)60136-0
oafree_for_read