Comparison of a VLP-based and GST-L1-based multiplex immunoassay to detect vaccine-induced HPV-specific antibodies in first-void urine.

Abstract

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 noninvasive 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 the 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). 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 bivalent 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). 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 = .0003; serum P ≤ .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti‐HPV6/11/16/18, r s = 0.85/0.86/0.91/0.79, P ≤ .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST‐L1‐MIA (FV urine anti‐HPV6/11/16/18, r s = 0.86/0.83/0.89/0.53, P ≤ .0001; serum anti‐HPV6/11/16/18, r s = 0.93/0.89/0.94/0.75, P ≤ .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive 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.