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

J Med Virol. 2020 Dec;92(12):3774-3783. doi: 10.1002/jmv.25841. Epub 2020 Apr 19.

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, rs = 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, rs = 0.86/0.83/0.89/0.53, P ≤ .0001; serum anti-HPV6/11/16/18, rs = 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.

Keywords: HPV antibodies; HPV serology; HPV vaccines; human papillomavirus; urine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / urine
  • Capsid Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay* / methods
  • Female
  • Glutathione Transferase / immunology
  • Glutathione Transferase / urine
  • Humans
  • Immunoassay / methods
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / immunology
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Infections* / urine
  • Papillomavirus Infections* / virology
  • Papillomavirus Vaccines* / administration & dosage
  • Papillomavirus Vaccines* / immunology
  • Vaccines, Virus-Like Particle / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • Papillomavirus Vaccines
  • Vaccines, Virus-Like Particle
  • Glutathione Transferase
  • Capsid Proteins