CROSS-PROTECTION OF MICE AGAINST A GLOBAL SPECTRUM OF RABIES VIRUS VARIANTS
CROSS-PROTECTION OF MICE AGAINST A GLOBAL SPECTRUM OF RABIES VIRUS VARIANTS
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DOI：
10.1128/jvi.69.8.4957-4962.1995
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发表时间：
1995-08-01
影响因子：
5.4
通讯作者：
EWALT, LC
中科院分区：
文献类型：
--
作者：
LODMELL, DL;SMITH, JS;EWALT, LC
狂犬病是一个持续的世界性问题，每年造成数万人和数百万只动物死亡。这一问题在发展中国家最为严重，在这些国家，人们负担不起细胞培养衍生的疫苗，而现有的神经组织衍生疫苗的免疫原性往往令人怀疑，并可能产生神经系统并发症。为了确定开发具有全球适用性的疫苗的可行性，我们研究了表达狂犬病病毒攻毒株（CVS）的糖蛋白（G）、核蛋白（N）或G和N（GN）的重组牛痘病毒是否会交叉保护小鼠免受代表全球发现的狂犬病病毒变异谱的17种狂犬病病毒分离株的侵害。结果与市售的人二倍体细胞疫苗（HDVC）进行了比较。在注射了17种病毒中的任何一种的小鼠中，大于或等于95%的小鼠通过接种表达G或GN的重组病毒而受到保护，大于或等于85%的小鼠受到HDCV的保护。表达N的重组病毒的保护性较低，仅对17种病毒中的11种提供保护。针对疫苗中使用的菌株G制备的抗体中和了所有17种病毒，并且来自感染任何一种病毒变体的小鼠的血清交叉中和了所有其他病毒，因此，未鉴定出可能导致疫苗失效的抗原差异。这些研究表明，单一的狂犬病病毒株或其G将在全球范围内保护野生型狂犬病病毒。
Rabies, a continuing worldwide problem, kills tens of thousands of people and millions of animals each year. The problem is most severe in developing countries, where cell culture-derived vaccines are unaffordable and the available nervous tissue-derived vaccines are often of questionable immunogenicity and may produce neurological complications. To determine the feasibility of developing a vaccine with worldwide applicability, we investigated whether recombinant vaccinia viruses expressing either the glycoprotein (G), the nucleoprotein (N), or both the G and N (GN) of the challenge virus strain (CVS) of rabies virus would cross protect mice against 17 rabies virus isolates representing the spectrum of rabies virus variants found worldwide. The results were compared with the commercially available human diploid cell vaccine (HDVC). Among mice injected with any of the 17 viruses, greater than or equal to 95% were protected by vaccination with recombinant viruses expressing G or GN, and greater than or equal to 85% of the mice were protected by the HDCV. The recombinant virus expressing N was less protective, protecting against only 11 of the 17 viruses. Antibody prepared against the G of the strains used in the vaccines neutralized all 17 viruses, and sera from mice infected with any one virus variant cross-neutralized all of the other viruses, Thus, no antigenic differences that would potentiate vaccine failures were identified. These studies suggest that a single rabies virus strain or its G would protect globally against wild-type rabies viruses.