Assessing high-throughput surrogate assays for real-world HPV16- and HPV18-specific vaccine immune monitoring: a comparison of PBNA, cCLIA, and IgG.

Introduction: Serological monitoring is needed for the real-world evaluation of immune responses after human papillomavirus (HPV) vaccination, but the pseudovirion-based neutralization assay (PBNA) is difficult to apply at scale. Methods: This study compared PBNA, competitive chemiluminescent immunoassay (cCLIA), and a virus-like particle-based indirect IgG immunoassay for HPV16- and HPV18-specific antibody assessment. The cross-sectional component included fully vaccinated recipients and unvaccinated controls, while the longitudinal component included adolescent girls receiving a two-dose bivalent HPV vaccine. Correlation, classification performance, systematic bias, and agreement were evaluated. Results: All three assays reflected HPV16/HPV18-specific vaccine-induced antibody response trends. cCLIA showed a more stable relationship with PBNA results than the IgG assay, especially in longitudinal monitoring and after the second dose. Although the IgG assay showed lower stability than cCLIA for PBNA-defined functional classification, it consistently captured the overall pattern of vaccine-induced antibody responses at the population level. Persistent numerical differences indicated that the high-throughput assays were not directly interchangeable with neutralization titers. Discussion: These findings support a stratified strategy for HPV16- and HPV18-specific immune monitoring using PBNA as a functional laboratory reference, cCLIA for high-throughput surrogate assessment, and IgG testing for population-level trend monitoring.