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Persistence of immune responses to the HPV ‐16/18 AS 04‐adjuvanted vaccine in women aged 15–55 years and first‐time modelling of antibody responses in mature women: results from an open‐label 6–year follow‐up study
Author(s) -
Schwarz T,
Spaczynski M,
Kaufmann A,
Wysocki J,
Gałaj A,
Schulze K,
Suryakiran P,
Thomas F,
Descamps D
Publication year - 2015
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/1471-0528.13070
Subject(s) - immunogenicity , medicine , antibody , adverse effect , immune system , immunology , persistence (discontinuity) , geotechnical engineering , engineering
Objective Evaluation of the long‐term HPV ‐16/18 AS 04‐adjuvanted vaccine immunogenicity persistence in women. Design Multicentre, open‐label, long‐term follow‐up ( NCT 00947115) of a primary phase– III study ( NCT 00196937). Setting Six centres in Germany and Poland. Population 488 healthy women (aged 15–55 years, age‐stratified into groups: 15–25, 26–45, and 46–55 years) who received three vaccine doses in the primary study. Methods Immune responses were evaluated in serum and cervicovaginal secretion ( CVS ) samples 6 years after dose 1. Anti‐ HPV ‐16/18 geometric mean titres ( GMT s) were measured by enzyme‐linked immunosorbent assay ( ELISA ), and were used to fit the modified power‐law and piecewise models, predicting long‐term immunogenicity. Serious adverse events ( SAE s) were recorded. Main outcome measures Anti‐ HPV ‐16/18 seropositivity rates and GMT s 6 years after dose 1. Results At 6 years after dose 1, all women were seropositive for anti‐ HPV –16 and ≥97% were seropositive for anti‐ HPV –18 antibodies. GMT s ranged from 277.7 to 1344.6 EU /ml, and from 97.6 to 438.2 EU /ml, for anti‐ HPV –16 and anti‐ HPV –18, respectively. In all age groups, GMT s were higher (anti‐ HPV –16, 9.3–45.1‐fold; anti‐ HPV –18, 4.3–19.4‐fold) than levels associated with natural infection (29.8 EU /ml). A strong correlation between serum and CVS anti‐ HPV ‐16/18 levels was observed, with correlation coefficients of 0.81–0.96 (anti‐ HPV –16) and 0.69–0.84 (anti‐ HPV –18). Exploratory modelling based on the 6–year data predicted vaccine‐induced anti‐ HPV ‐16/18 levels above natural infection levels for at least 20 years, except for anti‐ HPV –18 in the older age group (piecewise model). One vaccine‐related and two fatal SAE s were reported. Conclusions At 6 years after vaccination, immune responses induced by the HPV ‐16/18 AS 04‐adjuvanted vaccine were sustained in all age groups.