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单次给予表达全长人类免疫缺陷病毒1型(HIV-1)(HXB2)Rev/Env或密码子优化的HIV-1(JR-FL)gp120的慢病毒载体可在小鼠体内产生持久的免疫反应。

A single administration of lentiviral vectors expressing either full-length human immunodeficiency virus 1 (HIV-1)(HXB2) Rev/Env or codon-optimized HIV-1(JR-FL) gp120 generates durable immune responses in mice.

作者信息

Buffa Viviana, Negri Donatella R M, Leone Pasqualina, Bona Roberta, Borghi Martina, Bacigalupo Ilaria, Carlei Davide, Sgadari Cecilia, Ensoli Barbara, Cara Andrea

机构信息

National AIDS Center, Department of Drugs and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

出版信息

J Gen Virol. 2006 Jun;87(Pt 6):1625-1634. doi: 10.1099/vir.0.81706-0.

Abstract

Genetic immunization using viral vectors provides an effective means to elicit antigen-specific cellular immune responses. Several viral vectors have proven efficacious in inducing immune responses after direct injection in vivo. Among them, recombinant, self-inactivating lentiviral vectors are very attractive delivery systems, as they are able to efficiently transduce into and express foreign genes in a wide variety of mammalian cells. A self-inactivating lentiviral vector was evaluated for the delivery of human immunodeficiency virus 1 (HIV-1) envelope sequences in mice in order to elicit specific immune responses. With this aim, BALB/c mice were immunized with a single injection of self-inactivating lentiviral vectors carrying either the full-length HIV-1(HXB2) Rev/Env (TY2-IIIBEnv) or the codon-optimized HIV-1(JR-FL) gp120 (TY2-JREnv) coding sequence. Both vectors were able to elicit specific cellular responses efficiently, as measured by gamma interferon ELISPOT and chromium-release assays, upon in vitro stimulation of splenocytes from BALB/c immunized mice. However, only the TY2-JREnv-immunized mice were able to elicit specific humoral responses, measured as anti-gp120 antibody production. These data provide the first evidence that a single, direct, in vivo administration of a lentiviral vector encoding a viral gene might represent a useful strategy for vaccine development.

摘要

使用病毒载体进行基因免疫提供了一种引发抗原特异性细胞免疫反应的有效手段。几种病毒载体已被证明在体内直接注射后能有效诱导免疫反应。其中,重组自失活慢病毒载体是非常有吸引力的递送系统,因为它们能够有效地转导并在多种哺乳动物细胞中表达外源基因。为了引发特异性免疫反应,对一种自失活慢病毒载体进行了评估,以在小鼠体内递送人类免疫缺陷病毒1(HIV-1)包膜序列。为此,用单次注射携带全长HIV-1(HXB2)Rev/Env(TY2-IIIBEnv)或密码子优化的HIV-1(JR-FL)gp120(TY2-JREnv)编码序列的自失活慢病毒载体对BALB/c小鼠进行免疫。通过γ干扰素ELISPOT和铬释放试验测定,在体外刺激来自免疫的BALB/c小鼠的脾细胞时,两种载体都能够有效地引发特异性细胞反应。然而,只有经TY2-JREnv免疫的小鼠能够引发特异性体液反应,以抗gp120抗体产生来衡量。这些数据首次证明,单次体内直接施用编码病毒基因的慢病毒载体可能是疫苗开发的一种有用策略。

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