柳叶刀：早期试验显示低剂量H5N1流感疫苗对人体安全有效

    根据《柳叶刀》（Lancet）杂志今天（2006年9月7日星期四）网上发表的一篇文献，一种为预防禽流感病毒（H5N1）感染而开发的疫苗能够以低剂量在健康人群产生安全的免疫反应。为了使更多人群能够在大流行时获得疫苗接种，需要有效的低剂量疫苗。
    全球数家制药公司正在进行大流行流感疫苗的开发和临床评价。在以往《柳叶刀》上发表的临床试验中，科学家发现含部分H5N1病毒抗原的疫苗，加佐剂（增强疫苗效果的一种添加剂）后需要30微克，接种两针才能在人体产生较好的免疫反应。在最近的试验中，中国研究人员检测了H5N1全病毒佐剂疫苗的有效性。按以往的经验，全病毒疫苗可以诱发更强的免疫反应，但也产生更多的副反应。
    试验人员将120名18-60岁志愿者随机分配到1.25, 2.5, 5, 或 10微克组，每组人员分别接受两针安慰剂或两针氢氧化铝佐剂全病毒疫苗。56天后发现所有组均产生抗H5N1的中和抗体，但产生免疫反应最好的是两针10微克组。10微克疫苗满足欧盟关于季节性流感疫苗注册的所有要求。局部的疼痛，肿和全身发热是本试验最普遍报告的副反应。但是，疫苗组和对照组报告的副反应发生率无差异。全病毒疫苗副反应发生率与裂解疫苗相似。
    本研究作者尹卫东（北京科兴生物制品有限公司，中国）说：“在大流行时，对流感疫苗的需求远远超过这些疫苗的生产能力，这种情况促使WHO鼓励基于抗原节约原则的研究，包括使用佐剂和全病毒疫苗。我们的试验表明使用这两种方法生产的H5N1疫苗安全性和免疫原性良好。”
    作者说还需要在包括老人和儿童等更多的人中，对氢氧化铝佐剂全病毒H5N1 疫苗进行测试。

原文：
EARLY TRIAL SHOWS H5N1 INFLUENZA VACCINE SAFE AND EFFECTIVE IN HUMANS AT LOW DOSES

A vaccine in development against the avian influenza H5N1 virus can produce a safe immune response in healthy people at low doses, according to an Online/Article published today (Thursday September 7, 2006) by The Lancet. Vaccines that are effective at low doses are needed because they would allow more people to be vaccinated in the event of a pandemic.

Vaccines against pandemic influenza are being developed and clinically assessed by several drug companies throughout the world. In a previous trial published by The Lancet, scientists found that 30 micrograms of a vaccine containing part of the H5N1 virus given in two doses with an adjuvant, an additive that can increase effectiveness, produced a good immune response in humans. In the latest trial, Chinese researchers tested the effectiveness of a vaccine that contains a modified version of the whole H5N1 virus plus adjuvant. Vaccines made of whole viruses are known to trigger greater immune responses but are also known to produce more side-effects.

The investigators randomly assigned 120 volunteers aged 18-60 years to receive two doses of a placebo or the whole-virus vaccine at 1.25, 2.5, 5, or 10 microgram doses plus adjuvant aluminium hydroxide. After 56 days they found that all the formulations produced neutralising antibodies against the virus but the best response was seen in the 10 microgram group after two doses. The 10 microgram vaccine met all the European regulatory requirements for the licensing of an influenza vaccine. Pain, swelling, and fever were the most commonly reported side-effects in the trial. However, there was no difference in the frequency of reported side-effects between the vaccine and placebo group. The frequency of side-effects with the whole virus vaccine was also similar to that seen with vaccines made out of virus particles.

Study author Weidong Yin (Sinovac Biotech co. Ltd, Beiing, China) states: “During a pandemic, the demand for influenza vaccines will far outstrip the manufacturing capacity of such vaccines, a situation that has led to WHO encouraging investigation into dose-sparing strategies, including the use of adjuvants and whole-virion vaccine. Our trial suggests that an H5N1 vaccine manufactured and formulated with both of these approaches is well tolerated and immunogenic.”

The authors say trials testing whole-virus H5N1 vaccine with the aluminium hydroxide adjuvant in larger numbers of individuals, including elderly and children, are needed.