Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection - Two randomized controlled trials
Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection - Two randomized controlled trials
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DOI：
10.1001/jama.282.4.331
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发表时间：
1999-07-28
影响因子：
120.7
通讯作者：
Straus, SE
中科院分区：
文献类型：
--
作者：
Corey, L;Langenberg, AGM;Straus, SE
背景在过去的30年中，单纯疱疹病毒2型（HSV-2）感染的血清阳性率和新生儿疱疹已大幅增加。设计两项随机、双盲、安慰剂对照的多中心试验，研究一种重组亚单位疫苗，该疫苗含有两种主要的HSV-2表面糖蛋白（gB（2）和gD（2））各30 μ g，在第0、1和6个月施用。对照受试者给予柠檬酸盐缓冲溶剂。参加者随访1年后的第三次immunosity.Setting和参与者我们招募了2393人从1993年12月10日至1995年4月4日，谁是HSV-2和人类免疫缺陷病毒血清阴性。一项试验有18个中心，共招募了531名HSV-2血清阴性的HSV-2感染者伴侣;另一项试验有22个中心，共招募了1862名在性传播疾病诊所就诊的患者。共2268个（94.8%）符合入选标准，并被纳入分析，其中1135例随机分配至安慰剂组，2012例随机分配至疫苗组。根据随机分组研究期间培养物中HSV-2的血清转换或分离定义。结果时间-事件曲线显示50%的在试验的最初5个月，疫苗接种者的接种率低于安慰剂接种者;然而，总体疫苗有效性为9%（95%置信区间，-29%至36%）。安慰剂组和疫苗组的HSV-2感染率分别为4.6和4.2/100患者年（P = 0.58）。对获得HSV-2感染的疫苗接种者的随访显示，疫苗接种对临床首次生殖器HSV-2发作的持续时间（疫苗组，中位数为7.1天;安慰剂组，6.5天; P> 0.10）或随后的再激活频率（疫苗组，中位数为0.2;安慰剂组，0.3; P> 0.10）没有显著影响。该疫苗诱导高水平的HSV-2特异性中和抗体在接种疫苗的人谁没有和没有发展生殖器herpes.Conclusions有效和持续的保护性收购HSV-2感染需要超过高滴度的特异性中和抗体。对性传播病毒的保护涉及长期暴露，需要比本研究中达到的更高程度的疫苗效力。
Context In the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic.Objective To evaluate the efficacy of a vaccine for prevention of HSV-2 infection.Design Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 mu g each of 2 major HSV-2 surface glycoproteins (gB(2) and gD(2)) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization.Setting and Participants We enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2-seronegative partners of HSV-2-infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine.Main Outcome Measure Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group.Results Time-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval, -29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P = .58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P > .10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P > .10). The vaccine induced high levels of HSV-2-specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes.Conclusions Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.