Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles
Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles
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DOI：
10.1093/jnci/djg018
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发表时间：
2003-08-06
影响因子：
10.3
通讯作者：
De Grandi, P
中科院分区：
文献类型：
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作者：
Nardelli-Haefliger, D;Wirthner, D;De Grandi, P
背景：在早期试验中，人乳头瘤病毒 16 (HPV16) 病毒样颗粒 (VLP) 疫苗已被证明对女性具有良好的耐受性、免疫原性和针对 HPV16 的保护作用，其中大多数女性正在服用口服避孕药。先前的研究尚未确定 HPV 免疫是否会导致人类生殖道中的特定抗体水平，或者这些水平是否会在避孕或排卵周期中发生变化。因此，我们测定了接种 HPV16 VLP 的女性宫颈分泌物中总抗体和特异性抗体的水平，并检查了月经周期和口服避孕药的使用对这些水平的影响。方法：对两组妇女进行了免疫接种，其中 7 名正在服用口服避孕药，11 名正在排卵。血清转化后，每周两次收集血清和宫颈分泌物，持续 5 周。通过酶联免疫吸附测定法测定总免疫球蛋白（IgG 和 IgA）和疫苗特异性 IgG。非参数统计分析用于确定组间 IgG 水平差异的统计显着性，并通过 Spearman 相关系数确定血清和宫颈特异性 IgG 水平之间的相关性。结果：所有参与者在免疫接种后，其宫颈分泌物中均出现可检测到的抗 HPV16 VLP IgG 滴度。避孕组参与者的宫颈特异性 IgG 以及总 IgG 和 IgAs 滴度在整个避孕周期中相对恒定。相比之下，排卵组参与者的宫颈特异性 IgG 以及总 IgG 和 IgAs 滴度在月经周期中有所不同，在增殖期最高，在排卵期下降约九倍，在黄体期增加约三倍。避孕组女性的血清和宫颈特异性 IgG 水平相关 (r = .86)，但排卵组女性则不相关 (r = .27)。结论：宫颈处相对较高滴度的抗HPV16抗体在疫苗功效方面是有希望的；然而，排卵前后抗体滴度的下降增加了 HPV16 VLP 疫苗在排卵期期间效果可能较差的可能性。
Background: In early-phase trials, a human papillomavirus 16 (HPV16) virus-like particle (VLP) vaccine has been shown to be well tolerated, immunogenic, and protective against HPV16 in women, most of whom were taking oral contraceptives. Previous studies have not determined whether HPV immunization results in specific antibody levels in the human genital tract or whether these levels might vary during contraceptive or ovulatory cycles. Therefore, we determined the levels of total and specific antibodies in the cervical secretions of women who had been immunized with HPV16 VLPs and examined the influence of the menstrual cycle and oral contraceptive use on these levels. Methods: Two groups of women were immunized, seven who were taking oral contraceptives and 11 who were ovulating. After seroconversion, serum and cervical secretions were collected twice weekly for 5 weeks. Total immunoglobulins (IgG and IgA) and vaccine-specific IgGs were determined by enzyme-linked immunosorbent assay. Nonparametric statistical analyses were used to determine the statistical significance of differences in IgG levels between groups, and correlations between serum- and cervical-specific IgG levels were determined by the Spearman correlation coefficient. Results: All participants developed detectable titers of anti-HPV16 VLP IgGs in their cervical secretions after immunization. The cervical titers of specific IgG and total IgGs and IgAs among participants in the contraceptive group were relatively constant throughout the contraceptive cycle. In contrast, the cervical titers of specific IgG and total IgGs and IgAs among participants in the ovulatory group varied during the menstrual cycle, being highest during the proliferative phase, decreasing approximately ninefold around ovulation, and increasing approximately threefold during the luteal phase. Serum- and cervical-specific IgG levels were correlated (r = .86) in women in the contraceptive group but not in women in the ovulatory group (r = .27). Conclusions: The relatively high titer of anti-HPV16 antibodies at the cervix is promising in terms of vaccine efficacy; however, the decrease in antibody titer around ovulation raises the possibility that the HPV16 VLP vaccine might be less effective during the peri-ovulatory phase.