Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years: a phase I trial
Feng-Cai Zhu, Chang-Gui Li, Hong-Xing Pan, Yi-Ju Zhang, Dan Bi, Hai-Wen Tang, Sanjoy Datta, Feng-Cai Zhu, Chang-Gui Li, Hong-Xing Pan, Yi-Ju Zhang, Dan Bi, Hai-Wen Tang, Sanjoy Datta
Abstract
Globally, about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection. A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples. The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions. This phase I trial (NCT00549900) assessed the safety, tolerability, and immunogenicity of the vaccine in Chinese. Thirty healthy Chinese females, aged 15 to 45 years with a median age of 29.5 years, received three doses of Cervarix in Months 0, 1, and 6. Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination. Serious adverse events, new onset of chronic diseases, and other medically significant conditions were recorded throughout this trial. As an exploratory objective, HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7. Pain at the injection site was the most frequently reported local symptom. Two subjects reported medically significant adverse events. Both cases were assessed as unrelated to vaccination by the investigator. In Month 7, 100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers. HPV-16/18 AS04-adjuvanted vaccine, evaluated for the first time in Chinese females, was generally well tolerated and immunogenic, as previously shown in global studies.
Conflict of interest statement
Conflict of interest: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf and declare that Drs Feng-Cai Zhu, Chang-Gui Li, Hong-Xing Pan, and Yi-Ju Zhang have received research grants for the study from GlaxoSmithkline Biologicals; Dan Bi, Sanjoy Datta, and Hai-Wen Tang are employees of GlaxoSmithkline Biologicals and have been awarded share options.
References
- Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J] CA Cancer J Clin. 2005;55(2):74–108.
- Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide [J] J Pathol. 1999;189(1):12–19.
- Bao YP, Li N, Wang H, et al. Study on the distribution of human papillomavirus types in cervix among Chinese women: a meta-analysis [J] Chin J Epidemiol. 2007;28(10):941–946.
- Chen W, Zhang X, Molijn A, et al. Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18 [J] Cancer Causes Control. 2009;20(9):1705–1713.
- De Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses [J] Virology. 2004;324(1):17–27.
- Muñoz N, Bosch FX, Castellsagué X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective [J] Int J Cancer. 2004;111(2):278–285.
- Cai HB, Ding XH, Zhou YF, et al. Risk factors for cervical cancer in China: a case-control study [J] Eur J Gynaec Oncol. 2008;29(1):72–75.
- [No authors listed] Women's health in rural China [J] Lancet. 2009;374(9687):358.
- Gakidou E, Nordhagen S, Obermeyer Z. Coverage of cervical cancer screening in 57 countries: low average levels and large inequalities [J] PLoS Med. 2008;5(6):e132.
- Descamps D, Hardt K, Spiessens B, et al. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials [J] Hum Vaccin. 2009;5(5):332–340.
- Giannini SL, Hanon E, Moris P, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only [J] Vaccine. 2006;24(33–34):5937–5949.
- Einstein MH, Baron M, Levin MJ, et al. Comparison of the immunogenicity and safety of Cervarix™ and Gardasil® human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years [J] Hum Vaccin. 2009;5(10):705–719.
- Paavonen J, Naud P, Salmeron J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women [J] Lancet. 2009;374(9686):301–314.
- De Carvalho N, Teixeira J, Roteli-Martins CM, et al. Sustained efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7.3 years in young adult women [J] Vaccine. 2010;28(38):6247–6255.
- Ngan H YS, Cheung AN, Tarn KF, et al. Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong [J] Hong Kong Med J. 2010;16(3):171–179.
- Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial [J] Lancet. 2004;364(9447):1757–1765.
- Schwarz TF, Spaczynski M, Schneider A, et al. Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years [J] Vaccine. 2009;27(4):581–587.
- Harper D, Gall S, Naud P, et al. Sustained immunogenicity and high efficacy against HPV-16/18 related cervical neoplasia: long-term follow up through 6.4 years in women vaccinated with Cervarix™ (GSK's HPV 16/18 AS04 candidate vaccine) [C]. Tampa, Florida. 39th Society of Gynecologic Oncologists Meeting; 2008.
- Agosti JM, Goldie SJ. Introducing HPV vaccine in developing countries—Key challenges and issues [J] N Engl J Med. 2007;356(19):1908–1910.
Source: PubMed