Development and calibration of an HPV serology secondary standard for measuring antibody responses in HPV vaccine trials: a preliminary report.

Standardized measurement and reporting of antibody (Ab) levels induced by human papillomavirus (HPV) vaccination are essential for evaluating immunogenicity data across HPV vaccine trials and serosurveillance studies. The Frederick National Laboratory for Cancer Research generated an HPV serology standard for normalizing assays measuring antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. A study was conducted with the aim to calibrate the HPV serology standard to World Health Organization (WHO) international standards (IS)s for HPV 16 (IS16) and HPV 18 (IS18), establishing it as a secondary standard for these types with unitages directly traceable to the ISs. The candidate was produced using anti-serum from recipients of the nonavalent HPV vaccine. Nine laboratories from seven countries participated in the study using pseudovirion-based neutralization assays (PBNAs) and Ab-binding assays to detect HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 neutralizing and IgG antibodies, respectively, to test a panel of coded samples across independent assays. The panel consisted of the candidate standard, seronegative samples, and plasma references derived from recipients of a bivalent vaccine, IS16, and IS18. The study showed that the between-laboratory variability of results for neutralizing antibodies or Ab-binding levels is reduced when values are expressed relative to those of the IS16, IS18, or candidate standard, allowing greater comparability between laboratories. Based on these findings, unitages were assigned to the calibrated HPV serology secondary standard: 904 IU/mL (HPV 16 PBNA), 365 IU/mL (HPV 18 PBNA), 508 IU/mL (HPV 16 Ab-binding), and 270 IU/mL (HPV 18 Ab-binding), and the calibrated candidate standard should be utilized by the scientific community to minimize the use of the WHO international standards and preserve its stock. The HPV serology secondary standard is available to the scientific community to help harmonize results between laboratories.IMPORTANCEA human papillomavirus (HPV) serology secondary standard derived from serum donated by recipients of the nonavalent HPV vaccine was calibrated in a multicenter international collaborative study using World Health Organization international standards for antibodies to HPV type 16 and HPV type 18. The secondary standard was assigned unitages in globally recognized International Units (IU)/mL and was demonstrated to harmonize results for neutralizing antibody and antibody-binding assays to detect HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 neutralizing and IgG antibodies, respectively, across laboratories. The HPV serology secondary standard is publicly available to HPV laboratories for calibrating assays and reporting antibody results in IU/mL. It is a critical resource for assay standardization, enabling the comparison of results across HPV vaccine immunogenicity studies and HPV serosurveillance studies. This fills an important standardization gap in HPV antibody reporting.