Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation

Journal article

Baraniak I, Gomes AC, Sodi I, Langstone T, Rothwell E, Atkinson C, Pichon S, Piras-Douce F, Griffiths PD, Reeves MB and Fullerton, C. (2019). Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation. EBioMedicine. 50 (19), pp. 45-54. https://doi.org/10.1016/j.ebiom.2019.11.005
AuthorsBaraniak I, Gomes AC, Sodi I, Langstone T, Rothwell E, Atkinson C, Pichon S, Piras-Douce F, Griffiths PD, Reeves MB and Fullerton, C.
Abstract

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.

Year2019
JournalEBioMedicine
Journal citation50 (19), pp. 45-54
PublisherElsevier
ISSN2352-3964
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ebiom.2019.11.005
Web address (URL)http://europepmc.org/abstract/med/31735553
Publication dates
Online15 Nov 2019
Publication process dates
Accepted06 Nov 2019
Deposited15 May 2023
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