EFFICACY AND SAFETY OF GD-ALUM/MPL VACCINE - GENITAL HEPES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。单纯疱疹病毒1型和2型（HSV-1和HSV-2）引起频繁的人类感染。HSV-1感染的常见表现是鼻子和/或嘴唇周围的发热水泡，而HSV-2的表现是刺激性或疼痛性生殖器溃疡，尽管这两种疱疹病毒感染的部位偶尔会颠倒。无症状感染和严重的疾病可以发生任何疱疹病毒类型，两种病毒迁移到中枢神经系统，在那里它们可以保持潜伏状态，并在应激或其他刺激后在原始部位引起感染的重新激活。虽然禁欲和避孕套可以减少生殖器疱疹的传播，抗病毒治疗可以暂时抑制局部感染，但HSV-2血清阳性的发生率继续上升。本研究是一项III期评价，评估疫苗gD-Alum/MPL降低最易感人群（HSV-1和HSV-2血清阴性的年轻成年女性）生殖器疱疹疾病和感染发生率的能力。本研究的主要目的是在最初对HSV-1和HSV-2（HSV 1-/2-）均呈血清阴性的健康成年女性中，评价试验用疱疹疫苗在第2个月（第2次给药后）至第20个月期间预防HSV-1或HSV-2引起的生殖器疱疹疾病的疗效。次要目的包括评价疫苗预防以下疾病的有效性：1.在第7个月（第3次给药后）至第20个月之间由HSV-1或HSV-2引起的生殖器疾病; 2. HSV-2感染（通过培养或血清转化确认）在第2个月和第20个月之间;和，3. HSV-2感染发生在7至20个月之间。其他目标包括评价：1。候选疫苗的安全性和反应原性; 2.在HSV-2血清转化后3 - 6个月，在感染的疫苗接种者与感染的对照疫苗接种者中降低HSV脱落频率和数量的疫苗功效; 3.疫苗在最初为HSV 1-/2-的健康成年女性中预防2至20个月期间HSV-1或HSV-2感染的功效; 4.在最初为HSV 1-/2-的健康成年女性中，疫苗在预防由HSV-2引起的生殖器疱疹疾病中的2个月至20个月的功效; 5.在随机选择的疱疹疫苗接受者的亚组中的疫苗免疫原性（gD ELISA抗体、HSV中和抗体、CMI评估[如γ IFN]）; 6.针对HSV-2生殖器疱疹疾病和针对HSV-2感染的免疫保护的相关性（gD ELISA抗体、HSV-2中和抗体和CMI的测量，例如在具有和不具有突破性生殖器HSV-2疾病或感染的匹配受试者中的γ-IFN产生）; 7.疱疹疫苗对生殖器HSV-2疾病复发频率的影响; 8.在HSV 1-/2-妇女中疫苗针对原发性口唇HSV-1和HSV-2疾病的功效; 9.在HSV 1-/2-妇女中疫苗针对原发性其他非生殖器HSV疾病（不包括口唇）的功效; 10.在2剂（2 - 6个月）和3剂（7 - 20个月）后针对生殖器疱疹（1型或2型）或HSV-2感染的疫苗效力;和，11.在最初为HSV 1-/2-的健康成年女性中，在第2个月（第2次给药后）至第20个月之间预防培养证实的由HSV-1或HSV-2引起的生殖器疱疹疾病的疫苗功效。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) cause frequent human infections. Common manifestations of HSV-1 infection are fever blisters around the nose and/or lips, while those of HSV-2 are irritating or painful genital ulcers, although locations of infections by the two herpesvirus types are occasionally reversed. Asymptomatic infection and severe disease can occur with either herpesvirus type, and both viruses migrate to the central nervous system where they can remain latent and cause reactivation of infection at the original site following periods of stress or other stimuli. Although sexual abstinence and condoms can reduce transmission of genital herpes and antiviral therapy can temporarily suppress local infection, the incidence of seropositivity for HSV-2 has continued to rise. The present study is a Phase III evaluation of the ability of a vaccine, gD-Alum/MPL, to reduce the incidences of genital herpes disease and infection in the most susceptible population, young adult women who are seronegative against both HSV-1 and HSV-2. The primary objective of this study is evaluation of the efficacy of the investigational herpes vaccine in the prevention of genital herpes disease caused by either HSV-1 or HSV-2 between months 2 (post 2nd dose) and 20 in healthy, adult women who were initially seronegative against both HSV-1 and HSV-2 (HSV 1-/2-). Secondary objectives include evaluations of vaccine efficacy for prevention of: 1. Genital disease caused by HSV-1 or HSV-2 between months 7 (post 3rd dose) and 20; 2. HSV-2 infection (confirmed by either culture or seroconversion) between months 2 and 20; and, 3. HSV-2 infection occurring between months 7 and 20. Other objectives include evaluation of: 1. The safety and reactogenicity of the candidate vaccine; 2. Vaccine efficacy at reducing the frequency and quantity of HSV shedding 3-6 months following HSV-2 seroconversion in infected vaccinees versus infected control vaccine recipients; 3. Vaccine efficacy in the prevention of HSV-1 or HSV-2 infection between months 2 and 20 in healthy adult women who were initially HSV 1-/2-; 4. Vaccine efficacy in the prevention of genital herpes disease caused by HSV-2 between months 2 and 20 in healthy adult women who were initially HSV 1-/2-; 5. Vaccine immunogenicity in a subset of randomly selected herpes vaccine recipients (gD ELISA antibodies, HSV neutralizing antibodies, CMI assessments [such as gamma IFN]); 6. Correlates of immune protection against HSV-2 genital herpes disease and against HSV-2 infection (gD ELISA antibody, HSV-2 neutralizing antibody, and measures of CMI such as gamma-IFN production among matched subjects with and without breakthrough genital HSV-2 disease or infection); 7. The impact of the herpes vaccine on the frequency of recurrent genital HSV-2 disease; 8. The efficacy of vaccine against primary oro-labial HSV-1 and HSV-2 disease in HSV 1-/2- women; 9. The efficacy of vaccine against primary other non-genital HSV disease (excluding oro-labial) in HSV 1-/2- women; 10. Vaccine efficacy against genital herpes (types 1 or 2) or HSV-2 infection after 2 doses (months 2-6) and after 3 doses (months 7-20); and, 11. Vaccine efficacy in the prevention of culture-confirmed genital herpes disease caused by either HSV-l or HSV-2 between months 2 (post 2nd dose) and 20 in healthy adult women who were initially HSV 1-/2-.