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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。单纯疱疹病毒1型和2型（HSV-1和HSV-2）经常引起人类感染。1型单纯疱疹病毒感染的常见表现是鼻子和/或嘴唇周围出现发热水泡，而2型单纯疱疹病毒感染的常见表现是刺激性或疼痛性生殖器溃疡，尽管两种疱疹病毒感染的部位偶尔会发生逆转。两种疱疹病毒类型均可发生无症状感染和严重疾病，两种病毒都可迁移到中枢神经系统，在那里它们可保持潜伏状态，并在应激或其他刺激期后引起原部位感染的重新激活。尽管禁欲和使用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2型单纯疱疹病毒血清阳性的发生率仍在继续上升。目前的研究是一项对gd -明矾/MPL疫苗在最易感人群（对HSV-1和HSV-2血清均阴性的年轻成年女性）中降低生殖器疱疹疾病和感染发生率的能力的III期评估。本研究的主要目的是评估研究性疱疹疫苗在预防HSV-1和HSV-2 （HSV 1-/2-）血清检测均阴性的健康成年女性在第2个月（第2剂后）至第20个月期间由HSV-1或HSV-2引起的生殖器疱疹疾病的疗效。次要目标包括评估疫苗预防以下疾病的效力：7个月（第三剂后）至20个月期间由1型或2型单纯疱疹病毒引起的生殖器疾病；2. 在第2个月至第20个月之间感染2型单纯疱疹病毒（经培养或血清转化证实）；, 3。2型单纯疱疹病毒感染发生在7个月至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，与感染对照疫苗接种者相比，疫苗在减少HSV脱落频率和数量方面的有效性；3. 在最初感染HSV 1-/2-的健康成年妇女中，疫苗预防HSV-1或HSV-2感染2 ~ 20个月的有效性；4. 在最初感染HSV 1-/2-的健康成年女性中，疫苗预防HSV-2引起的生殖器疱疹疾病在2 ~ 20个月间的有效性；5. 随机选择的一部分疱疹疫苗接种者的疫苗免疫原性（gD ELISA抗体、HSV中和抗体、CMI评估[如γ干扰素]）；6. 对HSV-2生殖器疱疹疾病和HSV-2感染的免疫保护的相关性（gD ELISA抗体，HSV-2中和抗体，CMI测量，如γ - ifn的产生，在有或没有突破生殖器HSV-2疾病或感染的匹配受试者中）；7. 疱疹疫苗对生殖器2型单纯疱疹病毒复发频率的影响；8. 单纯疱疹病毒1-/2型女性原发性口腔-唇部HSV-1和HSV-2病疫苗的疗效观察9. HSV 1-/2型妇女接种疫苗预防原发性其他非生殖器HSV疾病（不包括口腔-唇部）的疗效；10. 2剂（2-6个月）和3剂（7-20个月）后预防生殖器疱疹（1型或2型）或2型单纯疱疹病毒感染的疫苗效果；, 11。在最初感染HSV 1-/2-的健康成年女性中，疫苗预防由HSV- 1或HSV-2引起的培养证实的生殖器疱疹疾病2个月（第2剂后）至20个月的有效性。

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-.