Jade Pattyn1, Gitika Panicker2, Martina Willhauck-Fleckenstein3, Severien Van Keer1, Laura Téblick1, Zoë Pieters4,5, Wiebren A A Tjalma6, Veerle Matheeussen7, Pierre Van Damme1, Tim Waterboer3, Elizabeth R Unger2, Alex Vorsters1. 1. Centre for the Evaluation of Vaccination (CEV); Vaccine & Infectious Disease Institute (VAXINFECTIO); Faculty of Medicine and Health Sciences; University of Antwerp, Belgium. 2. Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), USA. 3. Infections and Cancer Epidemiology Group; Infections, Inflammation and Cancer Research Program; German Cancer Research Center (DKFZ), Germany. 4. Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID); Vaccine & Infectious Disease Institute (VAXINFECTIO); Faculty of Medicine and Health Sciences; University of Antwerp, Belgium. 5. Centre for Statistics; I-Biostat; Hasselt University, Belgium. 6. Multidisciplinary Breast Clinic, Unit Gynaecologic Oncology; Department of Obstetrics and Gynaecology, Antwerp University Hospital (UZA) (Belgium); Molecular Imaging, Pathology, Radiotherapy, Oncology (MIPRO); Faculty of Medicine and Health Sciences; University of Antwerp, Belgium. 7. Department of Microbiology, Antwerp University Hospital (UZA) (Belgium); Department of Medical Microbiology (LMM); Vaccine & Infectious Disease Institute (VAXINFECTIO); Faculty of Medicine and Health Sciences; University of Antwerp (Belgium); Department of Medical Biochemistry; Faculty of Pharmaceutical, Biomedical and Veterinary Sciences; University of Antwerp, Belgium.
Abstract
BACKGROUND: Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). METHODS: We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bi- or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs ). FINDINGS: As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine p = 0.0003; serum p ≤ 0.0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, p ≤ 0.001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, p ≤ 0.0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, p ≤ 0.0001). CONCLUSION: FV urine HPV antibody detection is comparable with both assays, further supporting this non-invasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
BACKGROUND: Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). METHODS: We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bi- or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs ). FINDINGS: As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine p = 0.0003; serum p ≤ 0.0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, p ≤ 0.001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, p ≤ 0.0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, p ≤ 0.0001). CONCLUSION: FV urine HPV antibody detection is comparable with both assays, further supporting this non-invasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Entities:
Keywords:
HPV Antibodies; HPV serology; HPV vaccines; Human papillomavirus; Urine
Authors: Laura Téblick; Severien Van Keer; Annemie De Smet; Pierre Van Damme; Michelle Laeremans; Alejandra Rios Cortes; Koen Beyers; Vanessa Vankerckhoven; Veerle Matheeussen; Renee Mandersloot; Arno Floore; Chris J L M Meijer; Renske D M Steenbergen; Alex Vorsters Journal: Molecules Date: 2021-04-01 Impact factor: 4.411