PDF(Pubmed)
Abstract：
Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.
摘要：
人乳头瘤病毒（HPV）预防性疫苗已被证明可有效预防新的感染，但它不能治疗现有的HPV感染或相关疾病。因此，在成年人中仍然有一个重要的HPV储存库，因为疫苗接种计划主要针对年轻女性。这个非随机化的主要目标，开放标签试验旨在评估Gardasil-9在HPV16/18阳性女性中的3剂方案是否可以降低其体液的感染能力.我们的目的是评估疫苗诱导的抗体是否可以中和存在于粘膜中的病毒体，从而防止感染性颗粒的释放和HPV传播给性伴侣。作为我们的主要终点,E1^E4-HaCaT模型将用于评估宫颈的感染率，肛门和口腔样本，从疫苗接种前后的妇女获得。HPVDNA阳性，病毒体生产,血清转换，渗出液中抗体的存在，将被评估为将感染性降低归因于疫苗接种。我们的研究将招募两个不同的未接种疫苗的成年女性队列（RIFT-HPV1和RIFT-HPV2）。RIFT-HPV1将包括具有HPV16/18宫颈测试阳性并且没有明显宫颈病变或符合保守治疗条件的宫颈病变的受试者。RIFT-HPV2将包括HPV16/18肛门试验阳性且无明显肛门病变或符合保守治疗条件的肛门病变的受试者。以及宫颈HPV16/18检测阳性和HPV相关外阴病变的女性。符合两个队列的纳入标准的受试者将被招募到主要队列中。RIFT-HPV1.三个剂量的Gardasil-9将在第1次访问（0个月）肌肉内给药，访视2（2个月）和访视3（6个月）。尽管预防性HPV疫苗不能消除预先存在的感染，我们的结果将确定HPV疫苗接种是否可以被视为通过减少病毒传播来预防HPV相关疾病的新的补充策略.试用注册：https://clinicaltrials.gov/ct2/show/NCT05334706。
