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目的了解2005年上海市及其邻近地区麻疹流行株的基因变异及其对抗原性的影响。方法从麻疹疑似患者咽拭子标本分离病毒,RT-PCR扩增麻疹流行株及目前使用的麻疹疫苗株血凝蛋白基因(H)全序列,分析其在核苷酸及氨基酸水平上的序列差异,同时与中国以往的麻疹病毒分离株进行比较,采用交叉中和试验分析其抗原性的变化。结果4株上海地区麻疹病毒流行株属于H基因组H1a基因型,与麻疹疫苗株(A基因型)基因相比,有91～99 bp不同,引起27～28个氨基酸改变,其中重要的具有生物活性的第240位氨基酸由丝氨酸突变为天冬酰胺酸,第481位由酪氨酸突变为天冬酰胺酸。麻疹患者恢复期血清对流行株中和抗体滴度是麻疹疫苗株的2.49倍(P<0.05)。急性期患者血清及初次免疫后血清(1～2岁幼儿)对疫苗株的中和抗体滴度分别是流行株的1.69倍和1.61倍。结论上海地区麻疹流行株与麻疹疫苗株属于不同的基因型,除2个功能位点氨基酸突变外,具有生物学和免疫学活性的位点多数未发生改变,麻疹疫苗株仍能完全中和流行株,中和能力略有下降,麻疹疫苗对预防麻疹野病毒的感染依然有效。
Objective To understand the genetic variation of measles epidemic strains and their effects on antigenicity in Shanghai and its neighboring areas in 2005. Methods The virus was isolated from the throat swab specimens of suspected measles patients. The complete sequence of the hemagglutinin gene (H) was amplified by RT-PCR from the measles vaccine strain and the present measles vaccine strain. The nucleotide and amino acid sequence differences were analyzed At the same time, it was compared with the previous isolates of measles virus in China. The cross-neutralization test was used to analyze the antigenic changes. Results Four Shanghai isolates of measles virus belonged to the H1 genotype of H genome. They differ from those of the measles vaccine strain (A genotype) by 91-99 bp, causing 27-28 amino acid changes, of which the most important is biological activity Of the 240th amino acid from serine to asparaginic acid, the first 481 from tyrosine to asparaginic acid. Measles patients with convalescent sera showed a 2.49-fold (p <0.05) neutralizing antibody titers to measles vaccine strains. The neutralizing antibody titers of the vaccine and the serum of the patients with acute phase (1 to 2 years old) were 1.69 times and 1.61 times higher than the epidemic strains respectively. Conclusion Measles epidemic strains and measles vaccine strains belong to different genotypes in Shanghai. Except for two amino acid mutations in amino acid sequence, most of the sites with biological and immunological activity did not change, and measles vaccine strains were still completely neutralized The strains and the neutralization ability decreased slightly. The measles vaccine was still effective in preventing the infection of the wild measles virus.