Schiller John T, Castellsagué Xavier, Villa Luisa L, Hildesheim Allan
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD, USA.
Vaccine. 2008 Aug 19;26 Suppl 10(Suppl 10):K53-61. doi: 10.1016/j.vaccine.2008.06.002.
This review focuses on recent publications of clinical trials of two prophylactic human papillomavirus (HPV) vaccines: Gardasil (Merck & Co., Inc., Whitehouse Station, NJ USA), a quadrivalent vaccine containing L1 virus-like particles (VLPs) of types -6, 11, 16, and 18, and Cervarix (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types -16 and 18. In efficacy trials involving young women, both vaccines produced outstanding efficacy against primary and secondary endpoints associated with the vaccine type HPVs and were highly and consistently immunogenic. Both had excellent safety records and, as expected, the most frequent vaccine-related adverse were mild to moderate injection site sequelae. No evidence of waning protection was observed after four years for endpoints examined ranging from incident infection to cervical intraepithelial neoplasia grade 3 associated with the vaccine type HPVs. Gardasil was also highly efficacious at preventing vaginal/vulvar lesions and genital warts. However, neither vaccine demonstrated therapeutic efficacy against prevalent infections or lesions, regardless of the associated HPV type. Cervarix has shown limited cross-protection against infection with specific closely related types while preliminary results of limited cross-protection have been presented for Gardasil. As expected, more limited efficacy was noted for both vaccines when women with prevalent infection were included or endpoints associated with any HPV type were evaluated. Immunological bridging trials involving adolescent girls and boys were also recently published. For both vaccines, serum VLP antibody levels in girls were non-inferior to those generated in young women and antibody response to Gardasil was also non-inferior in boys. The results of these studies have led to the approval of Gardasil and Cervarix by national regulatory agencies in a number of countries.
本综述聚焦于两种预防性人乳头瘤病毒(HPV)疫苗的近期临床试验出版物:佳达修(美国新泽西州白宫站默克公司生产),一种四价疫苗,含6、11、16和18型L1病毒样颗粒(VLP);以及希瑞适(比利时里森萨特葛兰素史克生物制品公司生产),一种二价疫苗,含16和18型VLP。在涉及年轻女性的疗效试验中,两种疫苗对与疫苗型HPV相关的主要和次要终点均产生了出色的疗效,且免疫原性高且一致。两者均有出色的安全记录,正如预期的那样,最常见的疫苗相关不良反应为轻度至中度注射部位后遗症。在长达四年的时间里,对于从感染发生到与疫苗型HPV相关的宫颈上皮内瘤变3级等所检测的终点,均未观察到保护作用减弱的迹象。佳达修在预防阴道/外阴病变和尖锐湿疣方面也具有高效性。然而,无论相关HPV类型如何,两种疫苗均未显示出对现患感染或病变的治疗效果。希瑞适对特定密切相关类型的感染显示出有限的交叉保护作用,而佳达修则公布了有限交叉保护作用的初步结果。正如预期的那样,当纳入现患感染的女性或评估与任何HPV类型相关的终点时,两种疫苗的疗效均更为有限。近期还发表了涉及青春期女孩和男孩的免疫桥接试验。对于两种疫苗,女孩血清VLP抗体水平不低于年轻女性所产生的水平,男孩对佳达修的抗体反应也不低于女孩。这些研究结果已促使许多国家的国家监管机构批准了佳达修和希瑞适。