Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector
Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector
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DOI：
10.1128/jvi.71.4.3031-3038.1997
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发表时间：
1997-04-01
影响因子：
5.4
通讯作者：
Johnston, RE
中科院分区：
文献类型：
--
作者：
Caley, IJ;Betts, MR;Johnston, RE
一种委内瑞拉马脑炎病毒（VEE）的分子克隆减毒株已被遗传配置为表达异源病毒蛋白的复制能力疫苗载体（N. L. Davis， K. W. Brown， R. E. Johnston， J，病毒学报，70:3781-3787,1996）。将人类免疫缺陷病毒1型（HIV-1）的基质/衣壳（MA/CA）编码域克隆到VEE载体中，以确定VEE载体刺激小鼠抗hiv免疫应答的能力。VEE-MA/CA载体在小仓鼠肾（BHK）细胞细胞质中快速复制，并表达大量抗原可识别的MA/CA蛋白。在BALB/e小鼠皮下注射后，该载体侵入并在引流淋巴组织中复制，在具有有效免疫活性的部位表达HIV-1 MA/CA。所有免疫小鼠血清中均存在抗ma /CA免疫球蛋白G （IgG）和IgA抗体，第二次加强接种后滴度升高。在接受两次皮下免疫的小鼠阴道洗液中检测到MA/CA特异性IgA抗体。用表达MA/CA的VEE载体免疫后检测特异性MA/CA的细胞毒t淋巴细胞反应。这些发现证明了VEE疫苗载体系统能够刺激全面的体液和细胞免疫反应，这种反应的多面性使VEE成为一种有吸引力的疫苗，用于免疫病毒感染，如HIV-1，其保护性免疫的相关性尚不清楚，但可能包括免疫系统的多个组成部分。
A molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE) has been genetically configured as a replication-competent vaccine vector for the expression of heterologous viral proteins (N. L. Davis, K. W. Brown, and R. E. Johnston, J, Virol. 70:3781-3787, 1996). The matrix/capsid (MA/CA) coding domain of human immunodeficiency virus type 1 (HIV-1) was cloned into the VEE vector to determine the ability of a VEE vector to stimulate an anti-HIV immune response in mice. The VEE-MA/CA vector replicated rapidly in the cytoplasm of baby hamster kidney (BHK) cells and expressed large quantities of antigenically identifiable MA/CA protein. When injected subcutaneously into BALB/e mice, the vector invaded and replicated in the draining lymphoid tissues, expressing HIV-1 MA/CA at a site of potent immune activity. Anti-MA/CA immunoglobulin G (IgG) and IgA antibodies were present in serum of all immunized mice, and titers increased after a second booster inoculation. IgA antibodies specific for MA/CA were detected in vaginal washes of mice that received two subcutaneous immunizations. Cytotoxic T-lymphocyte responses specific for MA/CA were detected following immunization with the MA/CA-expressing VEE vector. These findings demonstrate the ability of a VEE-based vaccine vector system to stimulate a comprehensive humoral and cellular immune response, The multifaceted nature of this response makes VEE an attractive vaccine for immunization against virus infections such as HIV-1, for which the correlates of protective immunity remain unclear, but may include multiple components of the immune system.