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本文旨在研究表达HIV-1中国流行株gp120基因的重组腺相关病毒疫苗在小鼠和恒河猴体内的免疫原性。用rAAV2/1-gp120免疫BALB/c小鼠和恒河猴,分别用ELISA和HIV-1假病毒中和试验检测免疫动物血清中HIV-1特异性IgG抗体水平和中和抗体水平,用ELISPOT方法和体内杀伤实验检测HIV-1特异性细胞免疫应答水平。结果显示在小鼠体内用rAAV2/1-gp120仅免疫一次就能诱导较高水平的IgG抗体,IgG抗体至少能持续21周,但没有检测到中和抗体。rAAV2/1-gp120在小鼠体内诱导微弱水平的HIV-1特异性细胞免疫应答。rAAV2/1-gp120在恒河猴体内诱导的HIV-1特异性细胞和抗体反应均很弱,且检测不到中和抗体。提示rAAV2/1载体在诱导抗体反应方面具有特殊优势,但若希望诱导HIV-1特异性中和抗体,则需要改造env基因以提高其免疫原性。
This article aims to study the immunogenicity of recombinant adeno-associated virus vaccine expressing the gp120 gene of the Chinese HIV-1 strain in mice and rhesus monkeys. BALB / c mice and rhesus monkeys were immunized with rAAV2 / 1-gp120, and the levels of HIV-1 specific IgG antibodies and neutralizing antibodies in sera of immunized animals were detected by ELISA and HIV-1 pseudovirus virus neutralization assay respectively. ELISPOT Methods HIV-1-specific cellular immune responses were tested by in vivo cytotoxicity assay. The results showed that immunization with rAAV2 / 1-gp120 alone in mice resulted in the induction of higher levels of IgG antibodies that lasted for at least 21 weeks but no neutralizing antibodies were detected. rAAV2 / 1-gp120 induced a weak level of HIV-1 specific cellular immune response in mice. HIV-1-specific cells and antibody responses induced by rAAV2 / 1-gp120 in rhesus monkeys were both weak and no neutralizing antibodies were detectable. It is suggested that the rAAV2 / 1 vector has a special advantage in inducing an antibody reaction, but if it is desired to induce HIV-1-specific neutralizing antibodies, the env gene needs to be modified to enhance its immunogenicity.