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Humoral responses to Cytomegalovirus glycoprotein B vaccine with MF59 adjuvant

Baraniak, Ilona Anna; (2017) Humoral responses to Cytomegalovirus glycoprotein B vaccine with MF59 adjuvant. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Solid organ transplant (SOT) patients are at risk of end-organ diseases such as pneumonitis, hepatitis or enteritis caused by HCMV. HCMV infection can occur via primary infection of a seronegative recipient or upon reinfection or reactivation in a seropositive transplant recipient. Seronegative recipients have the greatest risk of viraemia and disease, showing that pre-existing natural immunity provides substantial protection. This, in turn, underpins vaccination as a viable strategy to control HCMV in the transplant setting. To test this, a clinical trial with a vaccine based on HCMV glycoprotein B (gB) antigen plus MF59 adjuvant was performed in SOT awaiting transplantation. The study showed that antibody titres against the gB antigen were significantly increased in both seropositive and seronegative recipients of the vaccine in comparison to the patients who received placebo, and importantly, higher titres correlated directly with reduced viraemia post-transplant. The aim of my thesis was to identify the component of the specific humoral response responsible for this effect. In comparison with placebo recipients, I could find no evidence for the protection being due to induction of antibodies that mediate neutralisation, antibody dependent cellular cytotoxicity, or prevent cell to cell spread of virus in culture. In contrast, analysis of antigenic domains of gB bound by the antibodies revealed that vaccination of seropositive individuals enhanced antibody responses against antigenic domain 2 and that these correlated with reduced viraemia post-transplant. Antibodies against three other antigenic domains were induced by the vaccine, but did not correlate with protection. These results suggest that antigenic domain 2 should be an important component of future HCMV vaccines to boost pre-existing immune responses that protect from HCMV infection. The protection afforded to seronegatives remains unidentified, but could be explained if another antigenic domain on gB remains to be discovered.

Type: Thesis (Doctoral)
Title: Humoral responses to Cytomegalovirus glycoprotein B vaccine with MF59 adjuvant
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: HCMV, HCMV vaccine, gB HCMV
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/1574595
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