Title
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First-void urine : a reservoir of HPV-related biomarkers
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Author
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Abstract
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Effectively monitoring infection, disease, and immune response relies on the availability of appropriate samples. Recently, there has been a growing interest in first-void urine sampling, especially among females, as it allows for the non-invasive collection of urogenital tract secretions that have accumulated between the labia minora. In human papillomavirus (HPV) research, first-void urine shows promise for assessing virological, diagnostic, and immunological endpoints, presenting a valuable single-sample option for disease and vaccine monitoring. This thesis contributed to the optimization of the use of first-void urine as a non-invasive sample for monitoring HPV infection and vaccination. With the focus on virological endpoints (HPV DNA), we contributed to selecting an optimal combination of first-void urine collection volume and processing methods (Chapter 02-A). Since there is substantial evidence supporting the feasibility of using first-void urine for detecting virological endpoints, this thesis mainly focused on addressing knowledge gaps related to immunological endpoints. Here, we confirmed the stability of HPV-specific antibodies in first-void urine and showed compatibility of IgG storage with a preservative required to avoid DNA degradation (Chapter 03-A). We also showed usability of an in-house developed immunoassay (HPV16-DELFIA) for the detection of HPV16-specific antibodies in first-void urine and serum (Chapter 03-B). Furthermore, we were the first to demonstrate that first-void urine is a suitable tool for monitoring HPV vaccination with the 9vHPV in females and detecting HPV DNA simultaneously (Chapter 03-C). Additionally, we set up pilot experiments investigating if HPV vaccination could potentially block the spread of newly produced virions. In this part, we proved that local HPV-specific antibodies captured with first-void urine, remain neutralizing (Chapter 04-A). Furthermore, we provided crucial insights into optimal precipitation protocols for detecting and concentrating HPV pseudovirions in first-void urine, potentially extending to naturally occurring HPV virions (Chapter 04-B). In summary, this thesis significantly contributed to the implementation of first-void urine as a non-invasively collected multi-purpose sample for monitoring HPV infection and vaccine impact. First-void urine self-sampling supports broader public health initiatives, providing a feasible option for conducting large-scale screening programs, epidemiological studies, and vaccine trials. |
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Language
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English
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Publication
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Antwerpen
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Universiteit Antwerpen, Faculteit Geneeskunde en Gezondheidswetenschappen
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2024
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DOI
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10.63028/10067/2051350151162165141
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Volume/pages
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257 p.
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Note
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Vorsters, Alex [Supervisor]
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Delputte, Peter [Supervisor]
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Van Keer, Severien [Supervisor]
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Van Damme, Pierre [Supervisor]
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Full text (open access)
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