[转移帖]GSK公布单纯疱疹病毒疫苗临床研究结果

zhaox

原帖由论坛会员Rojjer发表于 2012-1-9 09:07 |

Efficacy Results of a Trial of a Herpes Simplex Vaccine
Robert B. Belshe, M.D., Peter A. Leone, M.D., David I. Bernstein, M.D., Anna Wald, M.D., Myron J. Levin, M.D., Jack T. Stapleton, M.D., Iris Gorfinkel, M.D., Rhoda L. Ashley Morrow, Ph.D., Marian G. Ewell, Sc.D., Abbie Stokes-Riner, Ph.D., Gary Dubin, M.D., Thomas C. Heineman, M.D., Ph.D., Joann M. Schulte, D.O., and Carolyn D. Deal, Ph.D. for the Herpevac Trial for Women

N Engl J Med 2012; 366:34-43January 5, 2012


Background
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.

Methods
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.

Results
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).

Conclusions
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.)

Supported by a contract with the National Institute of Allergy and Infectious Diseases (N01-AI-45250) and by GlaxoSmithKline.

Dr. Belshe reports serving as a board member of Vivaldi Biosciences, receiving consulting fees from GlaxoSmithKline, receiving consulting fees and lecture fees from MedImmune, and receiving lecture fees from Merck. Dr. Bernstein reports receiving lecture fees and royalties from GlaxoSmithKline. Dr. Dubin reports being an employee of and receiving stock and travel, accommodation, and meeting expenses from GlaxoSmithKline and receiving royalties from Pfizer. Dr. Gorfinkel reports receiving grants, consulting fees, travel expenses to meetings, fees for participating in review activities, equipment and technical assistance, lecture fees, and payment for developing educational presentations from GlaxoSmithKline, having stock equity in and serving as an investigator for GlaxoSmithKline, and serving as an investigator for AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Bayer, PharmaNet, Wyeth, Berlex, Lundbeck, and CombinatoRx. Dr. Heineman reports being an employee of GlaxoSmithKline and receiving stock equity in GlaxoSmithKline as part of his compensation. Dr. Leone reports receiving consulting fees and speaker fees from GlaxoSmithKline, lecture fees from Novartis and Abbott Diagnostics, and grant support from Genocea. Dr. Levin reports receiving consulting fees and grants from GlaxoSmithKline. Dr. Morrow reports receiving consulting fees from Roche. Dr. Schulte reports owning stock in Pfizer. Dr. Stapleton reports receiving grant support from GlaxoSmithKline. Dr. Wald reports receiving consulting fees from AiCuris and grant support from the Washington Vaccine Alliance.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

No other potential conflict of interest relevant to this article was reported.

________________________________________

2012年1月4日，据《每日科学》报道，根据发表于《新英格兰医学》（NEJM）杂志上的结果，一种研究性疫苗能保护一些女性免于两种单纯疱疹病毒之一的能引起生殖器疱疹的病毒的感染。

该疫苗部分有效地防止单纯疱疹病毒1型（HSV-1）的感染，但不能保护女性免受单纯疱疹病毒2型（HSV-2）的感染。接受研究性疫苗的女性中少于一半的人感染了HSV-1，比接受对照疫苗的女性相比，降低了58%。

"这是我们研究结果中一些非常好的消息，我们部分地成功了--保护妇女免受由HSV-1引起的生殖器疾病，"Robert Belshe说，医学博士，圣路易斯大学疫苗开发中心主任，论文的第一作者。

"这是朝着建设一个有效的疫苗保护免受疱疹病毒感染引起的生殖器疾病的道路上迈出了一大步。它为我们开发一种能对2种单纯疱疹病毒起作用的疫苗研究指明了方向。"

HSV-1和HSV-2都是疱疹病毒家族的成员。通常情况下，HSV-2引起生殖器部位的病变和水泡。HSV-1通常会引起口腔和嘴唇的疮，尽管越来越多的研究发现，HSV-1也能导致生殖器疾病。

目前还没有治疗手段或获批的疫苗用以防止生殖器疱疹病毒感染，它影响着美国约25％的女性，是最常见的传染病之一。一旦进入人体，单纯疱疹病毒便永久的驻留了下来。该病毒可引起受感染女性所生的婴儿出现严重的神经系统疾病甚至死亡，该病毒也是HIV性传播的危险因素。

研究性生殖器疱疹疫苗的临床试验是由美国国立过敏和传染病研究所（NIAID）与葛兰素史克（GSK）在美国及加拿大50个地点进行。

该研究招募了8323名18~30岁之间的未感染HSV-1或HSV-2的女性。她们被随机分配成要么接受三份剂量的研究性单纯疱疹病毒疫苗（由葛兰素史克公司开发）或接受一种A型肝炎疫苗（对照组疫苗）。

参与者随访20个月并仔细评估生殖器疱疹病的发生。此外，所有研究参与者均进行血液测试，以确定是否在试验过程中发生了无症状的HSV-1或HSV-2感染。研究人员发现，两个或三个剂量的研究性疫苗对由HSV-1引起的生殖器疱疹疾病提供了显著的保护。然而，研究性疫苗没有保护妇女免受HSV-2引起的生殖器疾病。

"我们对这些研究结果感到惊讶，"Belshe说，美国圣路易斯大学医学院传染病和免疫学教授。 "我们没有想到这种疱疹疫苗能对其中一种单纯性疱疹病毒有作用而不是另一种。我们还发现了一个令人惊讶的情况，相对于HSV-2，HSV-1是导致生殖器疾病更为常见的原因。"

HSV-1已经成为导致感染生殖器疾病的越来越普遍的原因，因为越来越多的夫妇进行口交。 HSV-1和HSV-2是通过直接接触传播--嘴-嘴、嘴-生殖器、生殖器-生殖器，即使当受感染的人没有任何症状时，Belshe 补充道。

研究人员正在对研究参与者的血清进行实验室检测，继续研究为什么疫苗能保护由HSV-1而非HSV-2所致的生殖器疾病。

Belshe 说，一种假说就是HSV-1比HSV-2更容易被抗体杀死。这意味着疫苗抗体可能会更好地工作作用于HSV-1，结果导致免受HSV-1而不是HSV-2的感染。

研究性疱疹疫苗的早期研究表明，它可以为未感染HSV-1或HSV-2而其性伴侣有生殖器疱疹疾病的女性提供保护。研究人员相信，造成在最近的临床试验中不同结果的原因可能与研究的不同人群有关。在早先的研究中妇女受保护作用可能是由在后面这项研究中不存在的免疫或行为因素所致。

"对科学发现进行反复的研究证实是非常重要的，这就是为什么我们要对疫苗开展一个大的慰剂对照试验，"Belshe 说。 "我们的发现证实了科学过程的有效性，你必须有良好的科学证据来证实某些东西确实管用。"（引自生物谷）

zhaox

ipsvirus发表于 2012-1-10 14:32 |

为什么只对HSV-1有用，对HSV-2没用啊？两者病毒建相差很大吗？

zhaox

Rojjer发表于 2012-1-11 11:44 |:

1和2分别是两个型别，基因同源性为50%。
HSV-1主要感染6月-2岁，HSV-2则是生殖器疱疹的主要病原体。