[转移帖] NEJM：疟疾疫苗即将进入最终阶段试验

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原帖由论坛会员zhangning发表于 2008-12-22 19:59

在研究表明一种候选疟疾疫苗将肯尼亚和坦桑尼亚的婴幼儿疟疾风险降低一半之后，7个非洲国家的1.6万名儿童即将在明年早些时候参与该疫苗的最终阶段试验。

下一步的试验将扩展到布基纳法索、加蓬、加纳、马拉维和莫桑比克。试验定于2009年3月开始。

来自两个东非临床试验的结果12月8日发表在了《新英格兰医学杂志》（NEJM）上，这两个试验使用的疫苗目前被称为RTS,S。

“这些结果促进了一种前景，即疫苗有能力保护非洲的婴幼儿不受疟疾感染，”该研究的作者之一、肯尼亚医学研究所设在Kilifi的地理医学研究中心的Ally Olotu说。

其中一项试验证明了该疫苗——它能在这种凭借血液传播寄生虫到达肝脏之前制止它们——可以纳入非洲国家标准的儿童免疫规划中，而不会影响其他疫苗的有效性或破坏它自身的有效性。

第二项试验证实了这种疫苗对婴儿的安全和有效性，并发现它能降低疟疾的感染率一半（53%）。

Olotu说，接下来的试验的参与者是6—12周的新生儿以及5—17个月的婴儿，这些试验将提供关于该疫苗的有效性和安全性的更多信息。

坦桑尼亚Ifakara卫生研究所的Salim Abdulla说，在肯尼亚和坦桑尼亚进行的最新试验证实了早先在冈比亚成年人以及莫桑比克的学龄前儿童身上进行的更小规模的试验，在这些试验中疫苗提供了18个月到4年的保护。（参见 莫桑比克开始疟疾疫苗试验）

然而，Abdulla说，目前没有在非洲生产这种疫苗的计划，而且没有关于它的可能成本的信息。他告诉本网站说，科学家正在和非政府组织以及卫生发展机构协商开展一个社会营销运动，从而迅速扩大该疫苗在世界卫生组织以及其它免疫接种项目中的应用。

“这些发现为我们打算在非洲的11个地点进行的III期临床试验建立了强有力的基础，”Abdulla说。他在坦桑尼亚的坦噶医学研究中心参与了这些试验。（
NEJM，359, 2521 (2008)，Philip Bejon，Lorenz von Seidlein

Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age

Philip Bejon, Ph.D., John Lusingu, Ph.D., Ally Olotu, M.B., Ch.B., Amanda Leach, M.R.C.P.C.H., Marc Lievens, M.Sc., Johan Vekemans, Ph.D., Salum Mshamu, M.D., Trudie Lang, Ph.D., Jayne Gould, Ph.D., Marie-Claude Dubois, M.Sc., Marie-Ange Demoitié, M.Sc., Jean-Francois Stallaert, B.Sc., Preeti Vansadia, M.H.S., Terrell Carter, M.H.S., Patricia Njuguna, M.D., Ken O. Awuondo, H.N.D., Anangisye Malabeja, M.D., Omar Abdul, M.D., Samwel Gesase, M.D., Neema Mturi, M.R.C.Paed., Chris J. Drakeley, Ph.D., Barbara Savarese, R.N., Tonya Villafana, Ph.D., W. Ripley Ballou, M.D., Joe Cohen, Ph.D., Eleanor M. Riley, Ph.D., Martha M. Lemnge, Ph.D., Kevin Marsh, F.R.C.P., and Lorenz von Seidlein, Ph.D.

Background Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure.

Methods We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5).

Results A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria.

Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants

Salim Abdulla, M.D., Ph.D., Rolf Oberholzer, M.D., Omar Juma, M.D., Sulende Kubhoja, M.D., M.M.E.D., Francisca Machera, A.M.O., Christopher Membi, A.D.M.L.S., Said Omari, D.M.L.T., Alwisa Urassa, B.P.A., Hassan Mshinda, Ph.D., Ajuza Jumanne, M.D., Nahya Salim, M.D., M.M.E.D., Mwanjaa Shomari, B.Sc., Thomas Aebi, M.D., David M. Schellenberg, M.D., Ph.D., Terrell Carter, M.H.S., Tonya Villafana, Ph.D., M.P.H., Marie-Ange Demoitié, M.Sc., Marie-Claude Dubois, M.Sc., Amanda Leach, M.R.C.P.C.H., Marc Lievens, M.Sc., Johan Vekemans, M.D., Ph.D., Joe Cohen, Ph.D., W. Ripley Ballou, M.D., and Marcel Tanner, Ph.D., M.P.H.

Background The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.

Methods In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.

Results At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7;