Schwarz Tino F, Galaj Andrzej, Spaczynski Marek, Wysocki Jacek, Kaufmann Andreas M, Poncelet Sylviane, Suryakiran Pemmaraju V, Folschweiller Nicolas, Thomas Florence, Lin Lan, Struyf Frank
Central Laboratory and Vaccination Centre, Klinikum Würzburg Mitte, Standort Juliusspital, Würzburg, Germany.
NZOZ Vitamed, Bydgoszcz, Poland.
Cancer Med. 2017 Nov;6(11):2723-2731. doi: 10.1002/cam4.1155. Epub 2017 Oct 5.
Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.
女性一生中大部分时间都面临人乳头瘤病毒（HPV）感染风险。预防性接种HPV-16/18疫苗后的保护持续时间尚不清楚。我们调查了初次接种时年龄在15至55岁之间的女性接种HPV-16/18 AS04佐剂疫苗（AS04-HPV-16/18疫苗）后的10年免疫反应和长期安全性。在III期主要研究（NCT00196937）中接受三剂AS04-HPV-16/18疫苗初次接种的女性被邀请参加年度评估，以评估长期免疫原性和安全性。使用酶联免疫吸附测定（ELISA）测量血清和宫颈阴道分泌物（CVS）中的抗HPV-16/18抗体。在整个随访期间记录严重不良事件（SAE）。初次接种后10年，所有年龄组中抗HPV-16的血清阳性率仍然很高（≥96.3%）。结果发现，15至25岁的女性中有99.2%抗HPV-18保持血清阳性，而26至45岁和45至55岁的女性分别为93.7%和83.8%。所有年龄组的几何平均滴度（GMT）均保持在自然感染水平以上。抗HPV-16和抗HPV-18滴度分别比自然感染后观察到的滴度至少高5.3倍和3.1倍，并预计在所有年龄组中持续高于自然感染水平≥30年。在第10年，15至25岁受试者的抗HPV-16/18抗体滴度仍高于先前研究中观察到的平台水平。血清和CVS中抗体滴度的相关系数分别为0.64（抗HPV-16）和0.38（抗HPV-18）。本研究得出结论，15至55岁接种疫苗的女性在初次接种后长达10年可引发持续的免疫原性，安全性可接受，表明对HPV具有长期保护作用。
