ANTIBODIES TO HPV CAPSID PROTEINS AS IMMUNITY CORRELATES

描述(改编自《调查者摘要》)：我们的 对HPV感染生物学的理解是，目前尚不清楚 感染HPV型病毒对随后的再次感染具有免疫力 同样的类型。敏感和特异的血清学检测的可用性 现在使用由HPV衣壳蛋白组成的病毒样颗粒(VLP)进行检测 使解决这一问题成为可能。研究以确定是否 抗衣壳蛋白抗体将预防人类感染 将与开发基于VLP的疫苗的努力相关，并可能 提供一种疫苗的抗衣壳抗体水平的估计 必须诱导才能起到保护作用。我们最近得到了 允许检测在三家大型医院登记的女性的血清样本 人乳头瘤病毒感染自然病史的前瞻性研究 赞助了她的，NIH赞助了WIHS，NCI赞助了瓜纳卡斯特 哥斯达黎加的项目。前两项研究包括艾滋病毒阳性和艾滋病毒 消极的女人。因为感染艾滋病毒的人可能是主要目标 对于HPV疫苗的人群来说，重要的是要知道 预先存在的抗HPV抗体对随后感染HPV的风险 对于这些妇女来说，与艾滋病毒阴性妇女的情况相同或不同。 参加三项研究的女性的招募血清将通过 HPV-16、-31、-18、-45、-6和-11 VLP抗体的酶联免疫吸附试验。这个 招募时的抗体状态将与发生的HPV感染有关 和/或疾病在4-7年的随访期内。以下是以下内容： 本提案中要解决的问题：(1)血清抗体 与频率降低的特定HPV类型相关的VLP 意外感染HPV型？(2)是HPV血清抗体 与发生感染的频率降低相关的类型 遗传关系密切的类型？(3)VLP的最低水平是多少？ 提供完全保护的抗体？(4)是针对VLP的血清抗体 与再感染有关，特征是病毒载量较低，时间较短 病毒脱落的持续时间和/或较低的细胞学异常风险 比抗体阴性妇女的感染发生率高吗？(5)血清 HIV血清阳性妇女中HPV VLP抗体与HIV的比较 血清阴性女性，与相同或更高的频率相关 是否发生HPV感染和/或疾病？(6)在HIV血清阳性的妇女中， 免疫缺陷的程度，由CD4+细胞计数来衡量，相反 与先前存在的抗VLP提供的保护程度相关 抗体？

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?