Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15–55 years

3007 Background: Although prevalence of oncogenic HPV infection is highest in women younger than 25, incident infection is estimated to occur in 5% - 10% of women aged 25–55. New infections decrease with age, but the proportion that persists is higher. Therefore, women over 25 also may benefit from HPV vaccination. In a primary Phase III study (GSK 105879/014), an HPV-16/18 AS04 cervical cancer vaccine candidate was highly immunogenic and well tolerated in women up to age 55. This extension study evaluates the persistence of immune response and safety through 18 months after the first vaccine dose. Methods: Healthy women aged 15–55 years in Germany and Poland who had received 3 doses of HPV-16/18 L1 AS04 VLP vaccine at months 0, 1, and 6 in the primary study were invited to participate in a follow-up extension (15–25 years [n=169], 26–35 years [n=83], 36–45 years [n=89], and 46–55 years [n=176]). Immunogenicity and safety were assessed up to 18 months after vaccination. Results: At 18 months, 100% of subjects remained seropositive for both antigens in all age groups. For HPV-16, GMCs were 2,220.1 in women 15–25, 1,276.9 in women 26–35, 905.6 in women 36–45, and 809.0 in women 46–55. For HPV-18, GMCs were 828.2 in women 15–25, 441.8 in women 26–35, 289.7 in women 36–45, and 275.5 in women 46–55. In women over 25, GMCs tended to be higher in those initially seropositive. In the oldest age group, HPV-16 and HPV-18 GMCs remained at least 10-fold higher than natural infection levels reported in another study.The HPV-16/18 AS04 vaccine was well tolerated among all age groups. Conclusions: The HPV-16/18 AS04 vaccine candidate was highly immunogenic and well-tolerated. As with other vaccines, an age- dependent decrease in GMCs was observed, but GMCs remained substantially higher than natural infection levels previously reported in women 15–25. More importantly, GMCs at month 18 for women over 25 remained in the same range as GMCs observed in another study in women 15- 25 that were associated with sustained efficacy up to 4.5 years. Thus, in women up to age 55, an HPV-16/18 AS04 vaccine may protect against new infections with oncogenic HPV types that can cause cervical cancer. [Table: see text]

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Long-term persistence of anti-HPV-16 and -18 antibodies induced by vaccination with the AS04-adjuvanted cervical cancer vaccine: Modeling of sustained antibody responses☆

Gynecologic Oncology ◽

10.1016/j.ygyno.2009.01.011 ◽

2009 ◽

Vol 115 (3) ◽

pp. S1-S6 ◽

Cited By ~ 105

Author(s):

Marie-Pierre David ◽

Koen Van Herck ◽

Karin Hardt ◽

Fabian Tibaldi ◽

Gary Dubin ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Vaccine ◽

Antibody Responses ◽

Hpv 16 ◽

Cervical Cancer Vaccine

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

Human Vaccines ◽

10.4161/hv.7.9.15999 ◽

2011 ◽

Vol 7 (9) ◽

pp. 958-965 ◽

Cited By ~ 26

Author(s):

Tino F. Schwarz ◽

Marek Spaczynski ◽

Achim Schneider ◽

Jacek Wysocki ◽

Andrzej Galaj ◽

...

Keyword(s):

Cervical Cancer ◽

Immune Response ◽

Cancer Vaccine ◽

Hpv 16 ◽

Cervical Cancer Vaccine

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Randomized Trial of the Immunogenicity and Safety of the Hepatitis B Vaccine Given in an Accelerated Schedule Coadministered with the Human Papillomavirus Type 16/18 AS04-Adjuvanted Cervical Cancer Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00539-10 ◽

2011 ◽

Vol 18 (9) ◽

pp. 1510-1518 ◽

Cited By ~ 15

Author(s):

Geert Leroux-Roels ◽

Edwige Haelterman ◽

Cathy Maes ◽

Jack Levy ◽

Fien De Boever ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Hepatitis B ◽

Cancer Vaccine ◽

Hepatitis B Vaccine ◽

Hpv 16 ◽

Adjuvanted Vaccine ◽

Human Papillomavirus Type 16 ◽

The Third ◽

Cervical Cancer Vaccine

ABSTRACTThe human papillomavirus type 16/18 (HPV-16/18) AS04-adjuvanted cervical cancer vaccine is licensed for females aged 10 years and above and is therefore likely to be coadministered with other licensed vaccines, such as hepatitis B. In this randomized, open-label study, we compared the immunogenicity of the hepatitis B vaccine administered alone (HepB group) or with the HPV-16/18 AS04-adjuvanted vaccine (HepB+HPV group) in healthy women aged 20 to 25 years (clinical trial NCT00637195). The hepatitis B vaccine was given at 0, 1, 2, and 12 months (an accelerated schedule which may be required by women at high risk), and the HPV-16/18 vaccine was given at 0, 1, and 6 months. One month after the third dose of hepatitis B vaccine, in the according-to-protocol cohort (n= 72 HepB+HPV;n= 76 HepB), hepatitis B seroprotection rates (titer of ≥10 mIU/ml) were 96.4% (95% confidence interval [CI], 87.5 to 99.6) and 96.9% (CI, 89.2 to 99.6) in the HepB+HPV and HepB groups, respectively, in women initially seronegative for anti-hepatitis B surface antigen (HBs) and anti-hepatitis B core antigen (HBc). Corresponding geometric mean titers of anti-HBs antibodies were 60.2 mIU/ml (CI, 40.0 to 90.5) and 71.3 mIU/ml (CI, 53.9 to 94.3). Anti-HBs antibody titers rose substantially after the fourth dose of hepatitis B vaccine. All women initially seronegative for anti-HPV-16 and anti-HPV-18 antibodies seroconverted after the second HPV-16/18 vaccine dose and remained seropositive up to 1 month after the third dose. Both vaccines were generally well tolerated, with no difference in reactogenicity between groups. In conclusion, coadministration of the HPV-16/18 AS04-adjuvanted vaccine did not affect the immunogenicity or safety of the hepatitis B vaccine administered in an accelerated schedule in young women.

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