一种更安全的天花疫苗

Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox

Nature 428, 182 - 185 (11 March 2004); doi:10.1038/nature02331

PATRICIA L. EARL1, JEFFREY L. AMERICO1, LINDA S. WYATT1, LEIGH ANNE ELLER2, J. CHARLES WHITBECK3, GARY H. COHEN3, ROSELYN J. EISENBERG3, CHRISTOPHER J. HARTMANN4, DAVID L. JACKSON4, DAVID A. KULESH4, MARK J. MARTINEZ4, DAVID M. MILLER4, ERIC M. MUCKER4, JOSHUA D. SHAMBLIN4, SUSAN H. ZWIERS4, JOHN W. HUGGINS4, PETER B. JAHRLING4 & BERNARD MOSS1

1 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445, USA
2 Henry M. Jackson Foundation, Rockville, Maryland 20850, USA
3 Schools of Dental and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
4 United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA

Correspondence and requests for materials should be addressed to B.M. (bmoss@nih.gov).

The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.

一种更安全的天花疫苗

去年，由于害怕天花病毒被恐怖分子用作生物武器，美国政府建议卫生工作者志愿接种天花疫苗。

该计划被证明是有争议的，因为有人对这种威胁的现实性表示怀疑，而且人们对该疫苗的安全性也比较担心。

据报道，美国“国家过敏与传染病研究院”（NIAID）院长Anthony S. Fauci说，天花病毒“可能是目前最不安全的人类疫苗”。因此，获得一种更安全的疫苗便成为一个重要目标。高度减弱的变性牛痘病毒安卡拉（MVA）是已经获准使用的天花疫苗Dryvax的一种替代品，后者也是从牛痘病毒获得的。要验证一种疫苗预防天花的能力当然已不再可能，所以研究人员用可能感染猴痘病毒的猕猴对MVA和Dryvax做了新的对比。MVA疫苗所诱导的免疫响应的强度和性质与Dryvax疫苗类似，而且是完全具有保护性的。

由NIAID主持的一项临床试验目前正在通过网站 http://www.clinicaltrials.gov/ 招募志愿者，目的是通过临床试验对由单剂量Dryvax和双剂量MVA所诱导的免疫响应进行比较。