Oral immunization with recombinant listeria monocytogenes controls virus load after vaginal challenge with feline immunodeficiency virus.
Oral immunization with recombinant listeria monocytogenes controls virus load after vaginal challenge with feline immunodeficiency virus.
复制标题
用重组单核细胞增生李斯特氏菌口服免疫可控制猫免疫缺陷病毒阴道攻击后的病毒载量。
DOI：
10.1128/jvi.78.15.8210-8218.2004
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发表时间：
2004
影响因子：
5.4
通讯作者：
Dean,GreggA
中科院分区：
文献类型：
--
作者：
Stevens,Rosemary;Howard,KristinaE;Nordone,Sushila;Burkhard,MaryJo;Dean,GreggA
重组单核细胞增生李斯特菌作为人类免疫缺陷病毒（HIV）的疫苗载体具有许多有吸引力的特性。表达 HIV Gag 的野生型和减毒李斯特菌菌株已被证明可在小鼠体内诱导长寿命的粘膜和全身 T 细胞反应。使用 HIV 的猫免疫缺陷病毒 (FIV) 模型，我们评估了重组 L。挑战系统中的单核细胞增多症。五只猫用重组L进行了免疫。单增胞菌，表达 FIV Gag 并提供表达 FIV Env 的 DNA 疫苗 (LMgag/pND14-Lc-env)。对照猫进行假免疫或用野生型L进行免疫。单核细胞增多症（LM-wt）。阴道攻击一年后，在用重组细菌免疫的猫的九种组织中均未检测到原病毒，但在 10 只对照动物中的 8 只中至少检测到一种组织。通过使用严格的共培养系统，从五只 LMgag/pND14-Lc-env 免疫猫中的四只猫的骨髓中分离出病毒，但需要去除 CD8+T 细胞，表明 CD8+T 细胞抑制病毒复制。对照动物的肠系膜淋巴结中 CD4:CD8 比率倒置，并且 CD4+ 和 CD8+ 肠上皮 T 细胞均被耗尽，而 LMgag/pND14-Lc-env 免疫的动物则没有表现出此类异常。在攻击前三只 LMgag/pND14-Lc-env 免疫的猫以及攻击后 1 年时所有五只猫中，阴道 FIV 特异性免疫球蛋白 A 均以高滴度存在。这项研究表明重组L.单增李斯特菌在 FIV 阴道攻击后可对病毒载量进行一定程度的控制。
RecombinantListeria monocytogeneshas many attractive characteristics as a vaccine vector against human immunodeficiency virus (HIV). Wild-type and attenuatedListeriastrains expressing HIV Gag have been shown to induce long-lived mucosal and systemic T-cell responses in mice. Using the feline immunodeficiency virus (FIV) model of HIV we evaluated recombinantL. monocytogenesin a challenge system. Five cats were immunized with recombinantL. monocytogenesthat expresses the FIV Gag and delivers an FIV Env-expressing DNA vaccine (LMgag/pND14-Lc-env). Control cats were either sham immunized or immunized with wild-typeL. monocytogenes(LM-wt). At 1 year after vaginal challenge, provirus could not be detected in any of the nine tissues evaluated from cats immunized with the recombinant bacteria but was detected in at least one tissue in 8 of 10 control animals. Virus was isolated from bone marrow of four of five LMgag/pND14-Lc-env-immunized cats by use of a stringent coculture system but required CD8+T-cell depletion, indicating CD8+T-cell suppression of virus replication. Control animals had an inverted CD4:CD8 ratio in mesenteric lymph node and were depleted of both CD4+and CD8+intestinal epithelial T cells, while LMgag/pND14-Lc-env-immunized animals showed no such abnormalities. Vaginal FIV-specific immunoglobulin A was present at high titer in three LMgag/pND14-Lc-env-immunized cats before challenge and in all five at 1 year postchallenge. This study demonstrates that recombinantL. monocytogenesconferred some control of viral load after vaginal challenge with FIV.