Persistence of immune responses to the HPV‐16/18 AS04‐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

Abstract

ObjectiveEvaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women.DesignMulticentre, open-label, long-term follow-up (NCT00947115) of a primary phase–III study (NCT00196937).SettingSix centres in Germany and Poland.Population488 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.MethodsImmune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) 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 (SAEs) were recorded.Main outcome measuresAnti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1.ResultsAt 6 years after dose 1, all women were seropositive for anti-HPV–16 and ≥97% were seropositive for anti-HPV–18 antibodies. GMTs 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, GMTs 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 SAEs were reported.ConclusionsAt 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups.

Efficacy, immunogenicity, and safety of the HPV‐16/18 AS04‐adjuvanted vaccine in Chinese women aged 18–25 years: event‐triggered analysis of a randomized controlled trial

“…The anti‐HPV‐16/18 antibody kinetics were also in line with previous observations . anti‐HPV‐16/18 levels at M24 remained several folds above the GMT plateaus associated with sustained protection at M45–50 in a previous efficacy study .…”

Six‐year multi‐centre, observational, post‐marketing surveillance of the safety of the HPV‐16/18 AS04‐adjuvanted vaccine in women aged 10–25 years in Korea

“…In other clinical trials and surveillance studies conducted in different countries such as Japan, the Netherlands and United Kingdom7, 8, 9, 10, 11, 12, 13, 14, 15, 24, 25, 26, 27, 28, 29, transient injection‐site pain lasting for less than 5 days 30 was consistently the most commonly occurring AE. The results of the present study now provide further evidence that the safety profile of the HPV‐16/18 AS04‐adjuvanted vaccine is similar when administered to women in Korea.…”

Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20–26 years)

“…13,24 In prior studies, young women who received 3 doses of the HPV vaccine (at 15 years of age or older) showed clinically significant levels of immunogenicity up to 6 years after administration. 25 Further, girls (9-13 years old) who received 3 doses were more likely to continue to have an immune response 36 months after vaccination compared to young women (16-26 years old) who received 3 doses, which may indicate that 3 doses is necessary among older adolescents and young adults. However, it is unknown what clinical threshold of immune response is needed to be effective.…”

“…Details about NHANES can be found elsewhere. 27 Our study included young adult women (20)(21)(22)(23)(24)(25)(26) was first approved for use in 2006, all women in this age range would have received the vaccine after 12 years of age. This age group was selected because few data are available on those vaccinated after the recommended age of 11-12 years.…”