First-void urine as a tool to assess HPV-specific antibody-virion interaction after Gardasil-9 vaccination (URVIVE): Study protocol
BELL M. 1, LIPOVAC M. 1, TÉBLICK L. 1, DE SMET A. 1, VAN KEER S. 1, DEWILDE K. 2, TUMMERS P. 3, SALIHI R. 3,4, TJALMA W. 5, VORSTERS A. 1
1 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; 2 Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium; 3 Department of Gynecology and Obstetrics, Ghent University Hospital, Ghent, Belgium; 4 Department of Gynecology and Obstetrics, AZ St. Lucas Hospital, Ghent, Belgium; 5 Multidisciplinary Breast Clinic, Gynaecological Oncology Unit, Department of Obstetrics and Gynaecology, Antwerp University Hospital (UZA), Molecular Imaging, Pathology, Radiotherapy, and Oncology (MIPRO), Faculty of Medicine and Health Sciences, Universi, Antwerp, Belgium
Background: Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer and a major contributor to other anogenital and oropharyngeal cancers worldwide. Although prophylactic HPV vaccines are proven highly effective when administered prior to exposure, their potential biological impact in women with an existing HPV infection remains poorly understood. Emerging evidence suggests that vaccine-induced neutralizing antibodies may reduce the infectivity of newly produced virions in HPV-positive women, potentially limiting autoinoculation, persistence, and transmission to sexual partners. However, studying these effects at the genital tract level has been hampered by the lack of non-invasive sampling tools and suitable infection models.
Objectives: The URVIVE trial aims to establish a first-void urine-based in vitro infection model to investigate how vaccine-induced and naturally produced HPV-specific antibodies affect viral infectivity in HPV-positive women vaccinated with Gardasil 9.
Methods: URVIVE is a multicenter, non-randomized, open-label vaccination trial in approximately 50 HPV16-positive adult women (18-45 years) in Belgium. Participants receive two doses of the Gardasil 9 vaccine and are followed for up to 24 months. First-void urine and serum samples are collected at multiple timepoints before and after vaccination. HPV virions and HPV-specific antibodies are isolated from first-void urine and tested in an in vitro infection model. Viral infectivity, neutralization capacity, and antibody levels are quantified over time, and HPV DNA detection is used to monitor genotype-specific infection dynamics.
Results: URVIVE will generate longitudinal data on HPV-specific antibody responses and antibody-virion interaction in first-void urine, establishing it as a convenient and non-invasive tool to study local genital tract immune responses.
Conclusions/implications: This study will provide first insights into potential mechanisms by which vaccination of HPV-infected women at older age could limit autoinoculation and transmission to sexual partners. Findings could have important implications for future cancer prevention strategies that complement existing vaccination and screening strategies by targeting ongoing viral spread beyond primary prophylaxis.