Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15-55 years

Abstract

The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15-55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15-55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15-55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15-25 (n=168), 26-45 (n=186) and 46-55 years (n=177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46-55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15-55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.

Figure 1

Subject disposition. n, number of subjects; 15–25 years, subjects 15–25 years of age at the time of first vaccine dose; 26–45 years, subjects 26–45 years of age at the time of first vaccine dose; 46–55 years, subjects 46–55 years of age at the time of first vaccine dose.

Figure 2

Antibody levels in women between 15 and 55 years of age initially seronegative for HPV-16 or HPV-18 antibodies (ATP immunogenicity cohort). GMT, geometric mean titer; Error bars, 95% confidence interval; 15–25 years, subjects 15–25 years of age at the time of first vaccine dose; 26–45 years, subjects 26–45 years of age at the time of first vaccine dose; 46–55 years, subjects 46–55 years of age at the time of first vaccine dose; Natural infection: GMTs of subjects from Study HPV-008 who were (a) HPV-16 or (b) HPV-18 DNA-negative and seropositive at baseline (i.e., who had cleared a natural infection. GMTs were (a) 29.8 EL.U/ml and (b) 22.7 EL.U/ml11; Plateau phase: GMTs of subjects from Study HPV-007 in women aged 15–25 years at Months 45–50 after the first vaccine dose (Total cohort). GMTs were (a) 397.8 EL.U/ml and (b) 297.3 EL.U/ml.

Figure 3

Study design. n, number of subjects.