Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia

The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that...

Full description

Bibliographic Details
Main Authors: Baraniak, Ilona, Kropff, Barbara, McLean, Gary R., Pichon, Sylvie, Piras-Douce, Fabienne, Milne, Richard S. B., Smith, Colette, Mach, Michael, Griffiths, Paul D., Reeves, Matthew B.
Format: Article
Language:English
Published: Oxford University Press for the Infectious Diseases Society of America 2018
Subjects:
Online Access:https://repository.londonmet.ac.uk/1376/1/JID_2018_correctedproof.pdf
_version_ 1804071669634957312
author Baraniak, Ilona
Kropff, Barbara
McLean, Gary R.
Pichon, Sylvie
Piras-Douce, Fabienne
Milne, Richard S. B.
Smith, Colette
Mach, Michael
Griffiths, Paul D.
Reeves, Matthew B.
author_facet Baraniak, Ilona
Kropff, Barbara
McLean, Gary R.
Pichon, Sylvie
Piras-Douce, Fabienne
Milne, Richard S. B.
Smith, Colette
Mach, Michael
Griffiths, Paul D.
Reeves, Matthew B.
author_sort Baraniak, Ilona
collection LMU
description The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB ELISA antibody levels whose titer correlated directly with protection against post-transplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients. We focussed on four key antigenic domains (AD) of gB; AD1, AD2, AD4 and AD5 measuring antibody levels in patient sera and correlating these with post-transplant HCMV viremia. Vaccination of seropositive patients significantly boosted pre-existing antibody levels against the immunodominant region AD1 as well as against AD2, AD4 and AD5. A decreased incidence of viremia correlated with higher antibody titers against AD2 but not with antibody titers against the other three ADs. Overall, these data support the hypothesis that antibodies against AD2 are a major component of the immune protection of seropositives seen following vaccination with gB/MF59 vaccine and identify a correlate of protective immunity in allograft patients.
first_indexed 2024-07-09T03:46:56Z
format Article
id oai:repository.londonmet.ac.uk:1376
institution London Metropolitan University
language English
last_indexed 2024-07-09T03:46:56Z
publishDate 2018
publisher Oxford University Press for the Infectious Diseases Society of America
record_format eprints
spelling oai:repository.londonmet.ac.uk:13762020-06-05T09:19:38Z http://repository.londonmet.ac.uk/1376/ Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia Baraniak, Ilona Kropff, Barbara McLean, Gary R. Pichon, Sylvie Piras-Douce, Fabienne Milne, Richard S. B. Smith, Colette Mach, Michael Griffiths, Paul D. Reeves, Matthew B. 570 Life sciences; biology The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB ELISA antibody levels whose titer correlated directly with protection against post-transplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients. We focussed on four key antigenic domains (AD) of gB; AD1, AD2, AD4 and AD5 measuring antibody levels in patient sera and correlating these with post-transplant HCMV viremia. Vaccination of seropositive patients significantly boosted pre-existing antibody levels against the immunodominant region AD1 as well as against AD2, AD4 and AD5. A decreased incidence of viremia correlated with higher antibody titers against AD2 but not with antibody titers against the other three ADs. Overall, these data support the hypothesis that antibodies against AD2 are a major component of the immune protection of seropositives seen following vaccination with gB/MF59 vaccine and identify a correlate of protective immunity in allograft patients. Oxford University Press for the Infectious Diseases Society of America 2018-03-08 Article PeerReviewed text en cc_by_nd https://repository.londonmet.ac.uk/1376/1/JID_2018_correctedproof.pdf Baraniak, Ilona, Kropff, Barbara, McLean, Gary R., Pichon, Sylvie, Piras-Douce, Fabienne, Milne, Richard S. B., Smith, Colette, Mach, Michael, Griffiths, Paul D. and Reeves, Matthew B. (2018) Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia. Journal of Infectious Diseases, 217 (12). pp. 1907-1917. ISSN 1537-6613 10.1093/infdis/jiy102
spellingShingle 570 Life sciences; biology
Baraniak, Ilona
Kropff, Barbara
McLean, Gary R.
Pichon, Sylvie
Piras-Douce, Fabienne
Milne, Richard S. B.
Smith, Colette
Mach, Michael
Griffiths, Paul D.
Reeves, Matthew B.
Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title_full Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title_fullStr Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title_full_unstemmed Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title_short Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia
title_sort epitope specific humoral responses to human cytomegalovirus glycoprotein b vaccine with mf59 anti ad2 levels correlate with protection from viremia
topic 570 Life sciences; biology
url https://repository.londonmet.ac.uk/1376/1/JID_2018_correctedproof.pdf
work_keys_str_mv AT baraniakilona epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT kropffbarbara epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT mcleangaryr epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT pichonsylvie epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT pirasdoucefabienne epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT milnerichardsb epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT smithcolette epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT machmichael epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT griffithspauld epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia
AT reevesmatthewb epitopespecifichumoralresponsestohumancytomegalovirusglycoproteinbvaccinewithmf59antiad2levelscorrelatewithprotectionfromviremia