Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
PLoS One. 2013;8(1):e53067. doi: 10.1371/journal.pone.0053067. Epub 2013 Jan 2.
Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays.
METHODOLOGY/PRINCIPAL FINDINGS: Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27-0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28-0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection.
CONCLUSIONS/SIGNIFICANCE: Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity.
已经开发出几种血清学检测方法来检测针对致癌性人乳头瘤病毒（HPV）16 型感染产生的抗体。通过各种检测方法测量的抗体水平与随后的 HPV 感染风险之间的关联可能不同。我们比较了先前基于病毒样颗粒（VLP）的直接酶联免疫吸附测定（ELISA）测量的 HPV16 特异性抗体水平与通过其他检测方法测量的水平，并评估了在不同检测水平下对 HPV16 感染的保护作用。
方法/主要发现：对哥斯达黎加 HPV 疫苗试验对照组中 388 名未接种疫苗的女性的重复入组血清样本进行了 HPV16 血清学检测，使用三种血清学检测方法：基于 VLP 的直接 ELISA；基于 VLP 的竞争性 Luminex 免疫测定（cLIA）；以及碱性磷酸酶蛋白中和测定（SEAP-NA）。我们通过计算采样调整后的比值比（OR）和基于 cLIA 的标准截断值的 HPV16 血清阳性率，评估了在四年随访期间，检测阳性率与随后 HPV16 感染风险之间的关系，结果显示，与血清阴性者相比，基于 cLIA 的 HPV16 血清阳性与随后 HPV16 感染的保护作用显著相关（OR=0.48，95%CI：0.27-0.86）。与血清阴性者相比，直接 ELISA 的最高血清阳性三分位抗体水平（OR=0.53，95%CI：0.28-0.90）和 SEAP-NA（OR=0.20，95%CI：0.06，0.64）也与 HPV16 感染的保护作用显著相关。
结论/意义：通过评估的三种血清学检测方法中的任何一种检测到的入组 HPV16 血清阳性与随后的感染保护有关，尽管免疫保护的截止值不同。我们定义了在自然感染后更好地测量和转化为保护性免疫的检测方法和血清阳性水平。
