Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation
Background: Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59...
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doaj-08a927984721435f8ea3079281257f122020-11-25T01:30:02ZengElsevierEBioMedicine2352-39642019-12-01504554Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantationIlona Baraniak0Ariane C. Gomes1Isabella Sodi2Toby Langstone3Emily Rothwell4Claire Atkinson5Sylvie Pichon6Fabienne Piras-Douce7Paul D. Griffiths8Matthew B. Reeves9Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomClinical Development, Sanofi Pasteur, Marcy l'Etoile, FranceResearch and Non-Clinical Safety, Sanofi Pasteur, Marcy l'Etoile, FranceInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United KingdomInstitute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom; Corresponding author.Background: Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43–50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined. Methods: We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0–90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens. Findings: Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses – neutralisation which was abrogated by pre-absorbing the sera with recombinant gB. Interpretation: We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation. Keywords: Cytomegalovirus, Vaccination, Antibody responses, Prime-boosthttp://www.sciencedirect.com/science/article/pii/S2352396419307467 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ilona Baraniak Ariane C. Gomes Isabella Sodi Toby Langstone Emily Rothwell Claire Atkinson Sylvie Pichon Fabienne Piras-Douce Paul D. Griffiths Matthew B. Reeves |
spellingShingle |
Ilona Baraniak Ariane C. Gomes Isabella Sodi Toby Langstone Emily Rothwell Claire Atkinson Sylvie Pichon Fabienne Piras-Douce Paul D. Griffiths Matthew B. Reeves Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation EBioMedicine |
author_facet |
Ilona Baraniak Ariane C. Gomes Isabella Sodi Toby Langstone Emily Rothwell Claire Atkinson Sylvie Pichon Fabienne Piras-Douce Paul D. Griffiths Matthew B. Reeves |
author_sort |
Ilona Baraniak |
title |
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation |
title_short |
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation |
title_full |
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation |
title_fullStr |
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation |
title_full_unstemmed |
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation |
title_sort |
seronegative patients vaccinated with cytomegalovirus gb-mf59 vaccine have evidence of neutralising antibody responses against gb early post-transplantation |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-12-01 |
description |
Background: Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43–50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined. Methods: We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0–90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens. Findings: Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses – neutralisation which was abrogated by pre-absorbing the sera with recombinant gB. Interpretation: We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation. Keywords: Cytomegalovirus, Vaccination, Antibody responses, Prime-boost |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419307467 |
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