OC 03-02PERSISTENCE OF IMMUNE RESPONSE 10 YEARS AFTER ADMINISTRATION OF THE HUMAN PAPILLOMAVIRUS (HPV)-16/18 AS04-ADJUVANTED VACCINE TO WOMEN AGED 15–55 YEARS

05. HPV prophylactic vaccines
T.F. Schwarz 1, A. Galaj 2, M. Spaczynski 3, J. Wysocki 4, A.M. Kaufmann 5, P.V. Suryakiran 6, N. Folschweiller 7, F. Thomas 7, L. Lin 7, F. Struyf 7.
1Stiftung Juliusspital, Central Laboratory and Vaccination Centre, Würzburg (Germany), 2NZOZ Vitamed, Bydgoszcz (Poland), 3Poznan University of Medical Sciences, Department of Gynecologic Oncology, Poznan (Poland), 4Poznan University of Medical Sciences, Department of Preventive Medicine, Poznan (Poland), 5Charité-Universitätsmedizin Berlin, Department of Gynecology, Berlin (Germany), 6GSK Pharmaceuticals India Ltd., Vaccine Value and Health Science, Bangalore (India), 7GSK Vaccines, Clinical Research and Development, Wavre (Belgium)

Background / Objectives

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.


Methods

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.


Results

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]).


Conclusion

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


References

(1Paavonen et al. Lancet 2007; 2Naud et al. Hum Vaccin Immunother 2014)