Abstract:
A modified coxsackievirus genome used as an attenuated vaccine is provided to reduce toxicity of coxsackievirus compared to the wild type by modifying some nucleotides, and produce the amount of antibodies similar as that of the wild type, so that disease caused by coxsackievirus is prevented. A modified coxsackievirus genome used as an attenuated vaccine in which the nucleotide encoding at least one tyrosine of ITAM(Immunoreceptor Tyrosine-based Activation sequence Motif) sequence of capsid protein expressed from the coxsackievirus genome is modified by the nucleotide encoding other amino acid is provided, wherein the ITAM sequence is present in VP2 region of coxsackievirus; the nucleotide encoding tyrosine is substituted by the nucleotide encoding phenylalanine; and the modified coxsackievirus genome is derived from CVB1, CVB2, CVB3, CVB4 and CVB5 and comprises the nucleotide sequence encoding modified VP2 peptide having the amino acid sequences of SEQ ID NO:13, 15 or 17 or the nucleotide sequence of SEQ ID NO:14, 16 or 18. The recombinant viral vector contains the modified coxsackievirus genome, at least one cloning site, at least one antibiotic-resistant gene and at least one replication origin. The vaccine composition comprises the recombinant viral vector and pharmaceutically acceptable carriers.
Abstract translation:提供用作减毒疫苗的改良柯萨奇病毒基因组,以通过修饰一些核苷酸来减少柯萨奇病毒与野生型相比的毒性,并产生与野生型相似的抗体量,从而防止由柯萨奇病毒引起的疾病。 用作减毒疫苗的修饰的柯萨奇病毒基因组,其中编码由柯萨奇病毒基因组表达的衣壳蛋白的ITAM(基于免疫受体酪氨酸的激活序列基序)的至少一个酪氨酸的核苷酸被编码其他氨基酸的核苷酸修饰, 其中所述ITAM序列存在于柯萨奇病毒的VP2区域中; 编码酪氨酸的核苷酸被编码苯丙氨酸的核苷酸取代; 并且修饰的柯萨奇病毒基因组衍生自CVB1,CVB2,CVB3,CVB4和CVB5,并且包含编码具有SEQ ID NO:13,15或17的氨基酸序列的修饰的VP2肽的核苷酸序列或SEQ ID NO: 重组病毒载体含有修饰的柯萨奇病毒基因组,至少一个克隆位点,至少一个抗生素抗性基因和至少一个复制起点。 疫苗组合物包含重组病毒载体和药学上可接受的载体。