Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation.
Adjuvants, Immunologic
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
Clinical Trials, Phase II as Topic
Cytomegalovirus
/ immunology
Cytomegalovirus Infections
/ blood
Enzyme-Linked Immunosorbent Assay
Humans
Immunization, Secondary
Immunocompromised Host
Neutralization Tests
Organ Transplantation
/ adverse effects
Polysorbates
Randomized Controlled Trials as Topic
Squalene
Time Factors
Vaccination
Viral Envelope Proteins
/ immunology
Viral Vaccines
/ administration & dosage
Viremia
/ prevention & control
Antibody responses
Cytomegalovirus
Prime-boost
Vaccination
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
16
07
2019
revised:
06
11
2019
accepted:
06
11
2019
pubmed:
19
11
2019
medline:
1
5
2020
entrez:
19
11
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 31735553
pii: S2352-3964(19)30746-7
doi: 10.1016/j.ebiom.2019.11.005
pmc: PMC6921368
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
MF59 oil emulsion
0
Polysorbates
0
Viral Envelope Proteins
0
Viral Vaccines
0
glycoprotein B, Simplexvirus
0
Squalene
7QWM220FJH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-54Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI051355
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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