This extended follow-up study evaluated long-term immunogenicity and safety of HPV-16/18 AS04-adjuvanted vaccine up to 10 years (Y) after administration of first vaccine dose in women aged 15–55Y.
This phase III, multi-centre, parallel, open-label study (NCT00947115) included women aged 15–25Y, 26–45Y and 46–55Y at the time of vaccination who received 3 doses of HPV-16/18 vaccine (at month 0,1,6) in study NCT00196937. Serum anti-HPV-16/18 antibody responses were assessed by ELISA and compared with natural infection1 and plateau levels2. Anti-HPV-16/18 antibodies were also assessed (by ELISA) in cervico-vaginal secretion (CVS) samples collected annually from volunteers and correlations with serum antibodies were determined. Fatal or vaccine-related serious adverse events (SAEs) were recorded throughout the study.
10Y after first vaccination, persistence of antibodies was observed in initially seronegative women of all age groups, with seropositivity rate ≥96.3% (anti-HPV-16) and ≥83.8% (anti-HPV-18). Geometric mean titres (GMTs) tended to decrease with increasing age at vaccination (anti-HPV-16 GMT=965.4 [95%CI: 802.2, 1161.8] in 15–25Y-olds [N=123], 334.4 [270.5, 413.5] in 26–45Y-olds [N=121], 157.4 [128.4, 193.1] EL.U/mL in 46–55Y-olds [N=107]; anti-HPV-18 GMT=321.1 [95%CI: 265.0, 389.1] in 15–25Y-olds [N=127], 115.4 [93.9, 142.0] in 26–45Y-olds [N=142], 69.7 [56.0, 86.8] EL.U/mL in 46–55Y-olds [N=130]). In all age groups, at Y10, for both antigens, GMTs were at least 3.1-fold higher than those after natural infection. In 15–25Y-olds, anti-HPV-16 GMT remained 2.3-fold higher than the plateau at equivalent time points in efficacy studies in women 15–25Y, while anti-HPV-18 GMT appeared similar to the plateau level. In older age groups, GMTs were similar or below the plateau. Women with detectable antibodies in their CVS (positivity rate: 53.8–70.7% [anti-HPV-16]; 34.6–45.0% [anti-HPV-18]) tended to have higher serum antibody titres than women with no CVS antibodies detected (serum anti-HPV-16 GMT=1414.3 vs 512.0 [15–25Y], 749.6 vs 204.5 [26–45Y], 608.3 vs 134.3 [46–55Y]; anti-HPV-18 GMT=667.7 vs 294.1 [15–25Y], 418.9 vs 84.4 [26–45Y], 334.9 vs 78.8 [46–55Y]). Correlations between antibody titres in serum and CVS were: R=0.6399 (anti-HPV-16), R=0.3819 (anti-HPV-18). 1 woman HPV-16-seropositive pre-vaccination reported cervical dysplasia and 2 reported fatal SAEs, not vaccine-related (leukaemia [1/194 at 45Y], lung neoplasm [1/171 at 62Y]).
Ten years after first vaccination, sustained immunogenicity of the HPV-16/18 vaccine was demonstrated in women aged 15–55 years at vaccination, with an acceptable safety profile.
Funding: GlaxoSmithKline Biologicals SA
(1Paavonen et al. Lancet 2007; 2Naud et al. Hum Vaccin Immunother 2014)