ANTIBODIES TO HPV CAPSID PROTEINS AS IMMUNITY CORRELATES

描述（改编自研究者摘要）：我们的一个差距 对HPV感染生物学的理解是， 感染HPV类型赋予免疫力，随后再感染 同一类型。 敏感性和特异性血清学 目前，使用由HPV衣壳蛋白组成的病毒样颗粒（VLP）的检测 使得解决这个问题成为可能。 研究以确定是否 抗衣壳蛋白抗体将防止人类感染 可能与开发基于VLP的疫苗的努力有关， 提供了一个估计水平的抗衣壳抗体， 为了保护自己必须进行引产 我们最近获得了 允许对三个大型研究机构招募的妇女的血清样本进行检测， HPV感染自然史的前瞻性研究 美国国立卫生研究院（NIH）赞助的HERS，美国国立卫生研究院（NIH）赞助的WIHS，美国国家癌症研究所（NCI）赞助的瓜纳卡斯特 哥斯达黎加的项目。 前两项研究包括HIV阳性和HIV 消极的女人 因为艾滋病毒感染者可能是主要目标 对于HPV疫苗接种的人群，重要的是要知道 预先存在的抗HPV抗体对后续HPV感染的风险 与HIV阴性妇女相同或不同。 将通过以下方法检测入组3项研究的女性的招募血清： 针对HPV-16、-31、-18、-45、-6和-11的VLP的抗体的ELISA。 的 招募时的抗体状态将与HPV感染事件相关 和/或疾病在4-7年的随访期内。 以下是 本建议中要解决的问题：（1）血清抗体是否 特定HPV类型的VLP与HPV感染频率降低相关。 感染HPV类型？ (2)是HPV的血清抗体 与事件感染频率降低相关的类型， 基因相近的类型？ (3)VLP的最低水平是多少 能提供全面保护的抗体吗 (4)VLP的血清抗体 与以较低病毒载量为特征的再感染相关， 病毒脱落持续时间和/或细胞学异常风险较低 抗体阴性女性的偶发感染率更高吗 (5)是血清 与HIV相比，HIV血清阳性女性中的HPV VLP抗体 血清阴性女性，与相同或更高频率的 HPV感染和/或疾病？ (6)在艾滋病毒血清反应阳性的妇女中， 免疫缺陷的程度，如通过CD 4+细胞计数测量， 与预先存在的抗VLP提供的保护程度相关 抗体吗？

DESCRIPTION (Adapted from the Investigator's Abstract): One gap in our understanding of the biology of HPV infection is that it is not known if infection with an HPV type confers immunity to subsequent reinfection with the same type. The availability of sensitive and specific serological assays using virus-like particles (VLPs) composed of HPV capsid proteins now makes it possible to address this issue. Studies to determine whether anti-capsid protein antibodies will prevent infection in human populations would have relevance for efforts to develop VLP-based vaccines and may provide an estimate of the level of anti-capsid antibody that a vaccine would have to induce in order to be protective. We recently obtained permission to test serum specimens from women enrolled in three large prospective studies of the natural history of HPV infection; the CDC sponsored HERS, the NIH sponsored WIHS, and the NCI sponsored Guanacaste Project in Costa Rica. The former two studies include HIV positive and HIV negative women. Because HIV infected individuals may be a prime target population for an HPV vaccine, it is important to know if the relationship of pre-existing anti-HPV antibodies to the risk of subsequent HPV infection for these women is the same or different from that for HIV negative women. Recruitment sera from women enrolled in three studies will be tested by ELISA for antibodies to VLPs of HPV-16, -31, -18, -45, -6, and -11. The antibody status at recruitment will be related to incident HPV infection and/or disease over a follow-up period of 4-7 years. The following are the questions to be addressed in this proposal: (1) Are serum antibodies to VLPs of a particular HPV type associated with a decreased frequency of incident infection with that HPV type? (2) Are serum antibodies to an HPV type associated with a decreased frequency of incident infection with genetically closely related types? (3) What is the minimum level of VLP antibodies that confers full protection? (4) Are serum antibodies to VLPs associated with reinfections characterized by a lower viral load, shorter duration of viral shedding and/or lower risk of cytological abnormalities than that of incident infections in antibody negative women? (5) Are serum antibodies to HPV VLPs in HIV seropositive women, as compared to HIV seronegative women, associated with the same or a higher frequency of incident HPV infection and/or disease? (6) In HIV seropositive women, is the extent of immunodeficiency, as measured by CD4+ cell counts, inversely correlated with the degree of protection provided by pre-existing anti-VLP antibodies?