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
Publisher's version
License
File Access Level
Open
Permalink -

https://openresearch.lsbu.ac.uk/item/93zx8

Download files

Publisher's version
1-s2.0-S2352396419307467-main.pdf
License: CC BY 4.0
File access level: Open

  • 94
    total views
  • 30
    total downloads
  • 1
    views this month
  • 1
    downloads this month

Export as

Related outputs

Influenza H1N2 - first human case detected in the UK
Fullerton, C. (2024). Influenza H1N2 - first human case detected in the UK. The Biomedical Scientist Redactive Publishing Limited.
Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency
Rofael, S., Babe, C.L., Davrandi, M., Kondratiuk, A.L., Cleaver, L., Ahmed, N., Fullerton, C., McHugh, T. and Lowe, D.M. (2023). Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency. JAC-antimicrobial resistance. 5 (6), p. dlad135. https://doi.org/10.1093/jacamr/dlad135
Genomic and geographical structure of human cytomegalovirus
Charles, J., Venturini, C., Gantt, S., Atkinson, C., Griffiths, P., Goldstein, R.S. and Breuer, J. (2023). Genomic and geographical structure of human cytomegalovirus. PNAS. 120 (30), p. e2221797120. https://doi.org/10.1073/pnas.2221797120
A temperature dependent virus binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera
Gomes, A., Baraniak, I., McIntosh, M., Sodi, I., Langstone, T., Siddiqui, S., Fullerton, C., McLean, G., Griffiths, P. and Reeves, M. (2023). A temperature dependent virus binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera. Journal of General Virology. 104 (6). https://doi.org/10.1099/jgv.0.001860
In silico interrogation of the miRNAome of infected haematopoietic cells to predict processes important for human cytomegalovirus latent infection
Fullerton, C., Murray, M. J., Bradley, E., Ng, Y., Thomas, O., Patel, K., Angus, C. and Reeves, M. B. (2023). In silico interrogation of the miRNAome of infected haematopoietic cells to predict processes important for human cytomegalovirus latent infection. Journal of Biological Chemistry. 299 (6), p. 104727. https://doi.org/10.1016/j.jbc.2023.104727
The Cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
Gomes, A.C., Baraniak, I.A., Lankina, A., Holenya, P., Atkinson, C., Tang, G., Mahungu, T., Kern, F., Griffiths, P.D. and Reeves, M.B. (2023). The Cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread. Nature Communications. 14 (1), pp. 1-12. https://doi.org/10.1038/s41467-023-36683-x
Haplotype assignment of longitudinal viral deep sequencing data using covariation of variant frequencies.
Venturini C, Pang J, Tamuri AU, Roy S, Fullerton, C., Griffiths P, Breuer J and Goldstein RA (2022). Haplotype assignment of longitudinal viral deep sequencing data using covariation of variant frequencies. Virus Evolution. 8 (2), p. veac093. https://doi.org/10.1093/ve/veac093
HCMV carriage in the elderly diminishes anti-viral functionality of the adaptive immune response resulting in virus replication at peripheral sites.
Davies EL, Noor M, Lim EY, Houldcroft CJ, Okecha G, Atkinson C, Reeves MB, Jackson SE, Wills MR and Fullerton, C. (2022). HCMV carriage in the elderly diminishes anti-viral functionality of the adaptive immune response resulting in virus replication at peripheral sites. Frontiers in Immunology. 13. https://doi.org/10.3389/fimmu.2022.1083230
Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay.
Murray MJ, McIntosh M, Fullerton, C., Mahungu T, Wright E, Chatterton W, Gandy M and Reeves MB (2021). Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay. Journal of Infection. 82 (5), pp. 170-177. https://doi.org/10.1016/j.jinf.2021.03.010
Mixed cytomegalovirus genotypes in HIV-positive mothers show compartmentalization and distinct patterns of transmission to infants.
Pang J, Slyker JA, Roy S, Bryant J, Fullerton, C., Cudini J, Farquhar C, Griffiths P, Kiarie J, Morfopoulou S, Roxby AC, Tutil H, Williams R, Gantt S and Breuer J (2020). Mixed cytomegalovirus genotypes in HIV-positive mothers show compartmentalization and distinct patterns of transmission to infants. eLife. https://doi.org/10.7554/elife.63199
A comprehensive characterization of chronic norovirus infection in immunodeficient hosts.
Brown LK, Ruis C, Clark I, Roy S, Brown JR, Albuquerque AS, Patel SY, Miller J, Karim MY, Dervisevic S, Moore J, Williams CA, Cudini J, Moreira F, Lowe DM and Fullerton, C. (2019). A comprehensive characterization of chronic norovirus infection in immunodeficient hosts. Journal of Allergy and Clinical Immunology. 144 (5), pp. 1450-1453. https://doi.org/10.1016/j.jaci.2019.07.036
High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis.
Depledge DP, Cudini J, Kundu S, Atkinson C, Brown JR, Haque T, Houldcroft CJ, Koay ES, McGill F, Milne R, Whitfield T, Tang JW, Underhill G, Breuer J and Fullerton, C. (2018). High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis. Journal of Infectious Diseases. 218 (10), pp. 1592-1601. https://doi.org/10.1093/infdis/jiy358
A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology.
Fryer JF, Heath AB, Minor PD, Collaborative Study Group and Fullerton, C. (2016). A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology. Biologicals. 44 (4), pp. 242-251. https://doi.org/10.1016/j.biologicals.2016.04.005
Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes
Lassalle, F., Depledge, D.P., Reeves, M.B., Brown, A.C., Christiansen, M.T., Tutill, H.J., Williams, R.J., Einer-Jensen, K., Holdstock, J., Atkinson, C., Brown, J.R., van Loenen, F.B., Clark, D.A., Griffiths, P.D., Verjans, G.M.G.M., Schutten, M., Milne, R.S.B., Balloux, F., Breuer, J. and Fullerton, C. (2016). Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes. Virus Evolution. 2 (1). https://doi.org/10.1093/ve/vew017
Effects of donor/recipient human leukocyte antigen mismatch on human cytomegalovirus replication following liver transplantation.
Aldridge RW, Mattes FM, Rolando N, Rolles K, Smith C, Shirling G, Fullerton, C., Burroughs AK, Milne RS, Emery VC and Griffiths PD (2015). Effects of donor/recipient human leukocyte antigen mismatch on human cytomegalovirus replication following liver transplantation. Transplant Infectious Disease. https://doi.org/10.1111/tid.12325
Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.
Roxby AC, Fullerton, C., Asbjörnsdóttir K, Farquhar C, Kiarie JN, Drake AL, Wald A, Boeckh M, Richardson B, Emery V, John-Stewart G and Slyker JA (2014). Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women. PLoS ONE. https://doi.org/10.1371/journal.pone.0087855
Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination.
Lumley S, Fullerton, C. and Haque T (2013). Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination. Archives of Disease in Childhood. 99 (3). https://doi.org/10.1136/archdischild-2013-305511
Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.
Atabani SF, Smith C, Fullerton, C., Aldridge RW, Rodriguez-Perálvarez M, Rolando N, Harber M, Jones G, O'Riordan A, Burroughs AK, Thorburn D and Griffiths PD (2012). Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy. American Journal of Transplantation. 12 (9), pp. 2457-2464. https://doi.org/10.1111/j.1600-6143.2012.04087.x