【摘要】 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。更多还原

【Abstract】 Objective To study the hemagglutinin(H)gene variation and its effects on the antigenicity of wild type measles virus(MVW)isolated in Shanghai area in 2005.Methods The virus strains were isolated from pharyngeal swab samples.The complete H genes were amplified by reverse transcription-polymerase chain reaction(RT-PCR)and sequence analysis was conducted to compare the differences of nucleotide and amino acid between wild-type measles strains and vaccine strain (S191),and to compare with the previously isolated strains.A cross-neutralization test was performed to evaluate the antigenicity variations between the MVW and S191.Results The MVW was genotype Hla and there were 91-99 bp differences from vaccine strain gene(genotype A).The nucleotide differences resulted in 27-28 amino acids changes which leaded to amino acid substitution of asparagine for serine at position 240 and asparagine for tyrosine at position 481.Neutralization antibody geometric mean titer(GMT)against MVW was 2.49 times of that against S191 in the recovery measles cases(P<0.05).The GMT of the acute measles cases and the population(1-2 years old)primarily vaccinated against S191 was 1.69 and 1.61 times of that against MVW,respectively.Conclusions The genotype of the measles strains isolated in Shanghai area are different from measles vaccine strain.Although there were two important amino acid substitutions in the MVW,most of the biological and immunological amino acid sites of the MVW are the same as S191.The current vaccine S191 can neutralize MVW completely,but neutralizing ability decreases.Measles vaccine can effectively protect people from infected with MVW.更多还原