Efficacy results of a trial of a herpes simplex vaccine.
Efficacy results of a trial of a herpes simplex vaccine.
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DOI：
10.1056/nejmoa1103151
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发表时间：
2012-01-05
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影响因子：
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通讯作者：
Herpevac Trial for Women
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作者：
Belshe RB;Leone PA;Bernstein DI;Wald A;Levin MJ;Stapleton JT;Gorfinkel I;Morrow RL;Ewell MG;Stokes-Riner A;Dubin G;Heineman TC;Schulte JM;Deal CD;Herpevac Trial for Women
之前的两项针对 HSV 不一致的夫妇进行的含糖蛋白 D 的 2 型单纯疱疹病毒 (HSV-2) 亚单位疫苗的研究表明，对于 1 型 HSV (HSV-1) 和 HSV-2 抗体均为阴性的女性，其对生殖器疾病的疗效分别为 73% 和 74%。在男性或 HSV-1 血清阳性女性中未观察到疗效。我们进行了一项随机、双盲疗效现场试验，涉及 8323 名 18 至 30 岁的 HSV-1 和 HSV-2 抗体阴性女性。在第 0、1 和 6 个月，一些受试者接受了研究疫苗，该疫苗由 20 μg HSV-2 糖蛋白 D 以及明矾和 3-O-脱酰单磷酰脂质 A 作为佐剂组成；对照受试者接受了甲型肝炎疫苗，剂量为 720 酶联免疫吸附测定 (ELISA) 单位。主要终点是从第 2 个月（第 2 剂接种后 1 个月）到第 20 个月，出现由 HSV-1 或 HSV-2 引起的生殖器疱疹疾病。与对照疫苗相比，HSV 疫苗与局部反应风险增加相关，并引发 ELISA 和 HSV-2 中和抗体。总体而言，该疫苗并不有效；疫苗对生殖器疱疹疾病的功效为 20%（95% 置信区间 [CI]，-29 至 50）。然而，针对 HSV-1 生殖器疾病的疗效为 58%（95% CI，12 至 80）。疫苗针对 HSV-1 感染（有或无疾病）的功效为 35%（95% CI，13 至 52），但未观察到针对 HSV-2 感染的功效（-8%；95% CI，-59 至 26）。在代表 HSV-1 和 HSV-2 血清阴性女性一般人群的研究人群中，研究疫苗可有效预防 HSV-1 生殖器疾病和感染，但不能有效预防 HSV-2 疾病或感染。 （由国家过敏和传染病研究所和葛兰素史克资助；ClinicalTrials.gov 编号，NCT00057330。）
Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women. We conducted a randomized, double-blind efficacy field trial involving 8323 women 18 to 30 years of age who were negative for antibodies to HSV-1 and HSV-2. At months 0, 1, and 6, some subjects received the investigational vaccine, consisting of 20 μg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant; control subjects received the hepatitis A vaccine, at a dose of 720 enzyme-linked immunosorbent assay (ELISA) units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20. The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralizing antibodies to HSV-2. Overall, the vaccine was not efficacious; vaccine efficacy was 20% (95% confidence interval [CI], −29 to 50) against genital herpes disease. However, efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine efficacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (−8%; 95% CI, −59 to 26). In a study population that was representative of the general population of HSV-1– and HSV-2–seronegative women, the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; ClinicalTrials.gov number, NCT00057330.)