美国研究人员31日报告说,他们新开发出了一种抗非典实验疫苗。这种疫苗能有效阻止非典病毒在老鼠体内复制,其开发为最终研制出适用于人体的非典疫苗“迈出了关键一步”。
美国研究人员31日报告说,他们新开发出的一种疫苗在实验中有效地阻止了非典病毒在鼠体内复制。这一研究结果发表在4月1日正式出版的英国《自然》杂志上。
美国国家过敏和传染病研究所内贝尔博士领导的小组,以编码非典病毒表面一种外壳蛋白的DNA片段为基础开发出这种疫苗。这一片段本身不会引发感染,但能够刺激机体产生针对非典病毒的保护性免疫反应。研究人员还对疫苗中采用的DNA片段进行了修改,使其与病毒原始基因序列有所差别,以最大程度降低这种DNA片段与非典病毒或其他冠状病毒遗传材料发生重组的危险。
研究人员用两种不同形式的疫苗对总共10只鼠进行了实验,两种疫苗中的DNA在构成上略有区别,实验中还选取了5只接种了无效疫苗的鼠作为对照组,所有这些鼠在30天后分别接触非典病毒。分析结果发现,对照组中的实验鼠肺部存在大量非典病毒,而接种了两种疫苗的鼠肺部非典病毒水平分别都只有对照组的百万分之一左右,几乎可以忽略不计。
内贝尔在一份新闻公报中说,新实验结果是朝开发出对人体有效的非典疫苗迈出的关键一步。研究人员正在与位于美国加利福尼亚州的生物技术公司“Vical”合作,制造可用于人体临床试验的高纯化疫苗。目前,疫苗的人体临床试验尚有待美国食品和药物管理局批准。
一些未参与该项研究的专家指出,新疫苗的实验结果虽然令人鼓舞,但也不能过分夸大。采用DNA片段开发疫苗是一种较新的思路,此前科学家曾利用这种办法开发出一些针对其他病毒的疫苗,并在实验中刺激动物产生免疫反应,但迄今还没有一种DNA疫苗真正证明对人体有效。另外,目前用于研究非典病毒的动物模型有一定局限性,针对非典的DNA疫苗在投入人体临床试验前尚有很多研究工作要做。
SARS vaccine works well in mice
An experimental vaccine developed by federal researchers prevented the SARS (severe acute respiratory syndrome) coronavirus from reproducing in laboratory mice, according to a report published in the Apr 1 issue of Nature.
Gary J. Nabel(http://www.niaid.nih.gov/vrc/labs_nabel.htm,) of the National Institute of Allergy and Infectious Diseases (NIAID), one of the authors of the study, called the vaccine "a critical first step towards developing an effective human SARS vaccine." Nabel was quoted in a news release from the National Institutes of Health, of which NIAID is a part.
The NIAID noted that most vaccines use killed or weakened forms of a whole virus or bacteria. But the new vaccine contains a fragment of SARS virus DNA that codes for a protein on the outer surface of the virus, the agency said. The protein helps the virus enter host cells. Because the DNA in the vaccine codes only for the protein, it can’t cause infection by itself.
The investigators tested two versions of the vaccine in mice, the NIAID said. The two differed in how much genetic material was removed from the original piece of DNA. Two groups of five mice received three doses of one or the other form of the vaccine over 6 weeks. A control group of five mice received an inactive vaccine.
Thirty days later, all the mice were exposed to the SARS virus, the NIAID said. "After two days, the mice in the control group had very high levels of SARS virus in their lungs. The vaccinated mice had nearly negligible levels of SARS virus in their lungs." The controls had a million times as many virus particles as the vaccinated mice, the agency said.
The vaccine caused the mice to generate both antibodies and specialized T cells to defend against the SARS virus, the NIAID reported. But the researchers found that the antibodies alone caused the dramatic reduction in virus in the vaccinated mice.
NIAID Directory Anthony S. Fauci, MD, noted that the SARS coronavirus was identified only a year ago. "This [vaccine] research was done in a remarkably short period of time, a testament to the serious attention and great cooperation the public health community has displayed in response to SARS," he said in the news release.
In their report in Nature, the authors of the study say that DNA vaccines have proved successful in various animal experiments with several infectious diseases. But they add, "This approach has only recently been used in human studies, and its potential to protect against human diseases has yet to be established." In addition, mice are an imperfect model for SARS infections in humans. (Another recent NIAID study showed that unvaccinated mice could be infected with the SARS virus, but they developed antibodies that blocked viral replication.)
Consequently, the report says, it will be important to test whether the experimental SARS vaccine generates an immune response in humans. If the response is unsatisfactory, it could be augmented by using inactivated viral vaccine candidates or other techniques, the researchers say.
The NIAID’s DNA vaccine is one of several potential SARS vaccines under development. For example, Chinese health officials announced in January that they would launch the first human trial of a SARS vaccine developed in China. Also in January, it was reported that the University of British Columbia had developed three candidate SARS vaccines, which were to be tested in animals at the Southern Research Institute in Birmingham, Ala.
Yang Z, Kong W, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004(1 Apr);428:561-4 [Abstract]http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v428/n6982/abs/nature02463_fs.html