Van Damme Pierre, Leroux-Roels Geert, Simon Philippe, Foidart Jean-Michel, Donders Gilbert, Hoppenbrouwers Karel, Levin Myron, Tibaldi Fabian, Poncelet Sylviane, Moris Philippe, Dessy Francis, Giannini Sandra L, Descamps Dominique, Dubin Gary
Universiteit Antwerpen, Vaccine & Infectious Disease Institute, Centre for the Evaluation of Vaccination, Building R, 2nd Floor, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Center for Vaccinology, Ghent University and Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Vaccine. 2014 Jun 17;32(29):3694-705. doi: 10.1016/j.vaccine.2014.03.040. Epub 2014 Mar 25.
A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized, controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes, with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18-25 year-old women.
In one trial (NCT00231413), subjects received control or one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M) 0,1,6. In a second trial (NCT00478621), subjects received control or one of 5 tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or M0,6).
One month after the third injection (Month 7), there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing 20/20/10/10 μg VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20 μg VLPs for anti-HPV-16 antibodies. There was also a trend for lower HPV-16 and -18-specific memory B-cell responses for tetravalent AS04 vaccines versus control. No such trends were observed for CD4(+) T-cell responses. Immune interference could not always be overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different adjuvant system. All formulations had acceptable reactogenicity and safety profiles. Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs, especially for formulations containing AS01.
HPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune interference is a complex phenomenon that cannot always be overcome by changing the antigen dose or adjuvant system.
一种除针对16型和18型人乳头瘤病毒（HPV）外，还靶向致癌性HPV型别的预防性HPV疫苗，可能会扩大对宫颈癌的预防范围。开展了两项I/II期随机对照研究，以比较含有另外两种致癌基因型病毒样颗粒（VLP）的四价HPV L1 VLP研究性疫苗与已获许可的HPV-16/18 AS04佐剂疫苗（对照）在18至25岁健康女性中的免疫原性和安全性。
在一项试验（NCT00231413）中，受试者在第0、1、6个月接受对照疫苗或6种四价HPV-16/18/31/45 AS04疫苗配方中的一种。在第二项试验（NCT00478621）中，受试者接受对照疫苗或5种用不同佐剂系统（AS04、AS01或AS02）配制的四价HPV-16/18/33/58疫苗中的一种，按不同接种程序（第0、1、6个月或第0、3个月或第0、6个月）接种。
第三次注射后1个月（第7个月），与对照相比四价AS04佐剂疫苗的抗HPV-16和-18几何平均抗体滴度（GMT）有持续降低趋势。对于含20/20/10/10μg VLP的HPV-16/18/31/45 AS04疫苗，其抗HPV-16和抗HPV-18抗体的GMT在统计学上显著较低；对于含20/20/20/20μg VLP的HPV-16/18/33/58 AS04疫苗，其抗HPV-16抗体的GMT在统计学上显著较低。四价AS04疫苗与对照相比，HPV-16和-18特异性记忆B细胞反应也有降低趋势。CD4(+) T细胞反应未观察到此类趋势。增加HPV-16/18 L1 VLP剂量或使用不同佐剂系统并不总能克服免疫干扰。所有配方的反应原性和安全性均可接受。接种疫苗后7天内的反应原性往往会随着额外VLP的引入而增加。特别是对于含AS01的配方。
在HPV-16/18 AS04佐剂疫苗中添加额外的HPV L1 VLP时，HPV-16和-18抗体反应较低。免疫干扰是一种复杂现象，改变抗原剂量或佐剂系统并不总能克服。
