Polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response but is unable to provide sterilizing protection against heterologous Simian/human immunodeficiency virus infection in pigtailed macaques
Polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response but is unable to provide sterilizing protection against heterologous Simian/human immunodeficiency virus infection in pigtailed macaques
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DOI：
10.1128/jvi.75.5.2224-2234.2001
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发表时间：
2001-03-01
影响因子：
5.4
通讯作者：
Martin, MA
中科院分区：
文献类型：
--
作者：
Cho, MW;Kim, YB;Martin, MA
引发针对人类免疫缺陷病毒 1 型 (HIV-1) 分离株的广泛交叉反应性中和抗体 (NAb) 的巨大困难归因于其病毒包膜糖蛋白的几个内在特性，包括其复杂的四级结构、广泛的糖基化和显着的遗传变异性。大多数先前评估的候选疫苗都利用了来自单一病毒分离株的包膜糖蛋白。在这里，我们比较了用单一或多种病毒分离株衍生的包膜蛋白对猪尾猕猴进行疫苗接种后，NAb 的广度和保护性免疫反应。在用表达 gp160 的重组牛痘病毒引发并用来自 (1) LAI、RIF、89.6、ADS 和 Bal（多价）的 gp120 蛋白加强后，用猿猴/人类免疫缺陷病毒株 DH12 (SHTVDH12) 攻击动物； (ii) LAI、RF、89.6、AD8、Bal 和 DH12（多价-DH12）； (iii) 89.6（单价-89.6）； (iv) DH12（单价-DH12）。两个多价疫苗组中的动物比两个单价疫苗组中的动物产生了针对更多 HIV-1 分离株的 NAb（P = 0.0054）。然而，反应范围的扩大几乎完全针对疫苗株。对 SHIVDH12 的耐药性与攻击当天针对病毒的 NAb 水平密切相关 (P = 0.0008)。因此，单价 DH12 和多价 DH12 疫苗组中的动物比用缺乏 DH12 成分的制剂（即多价和单价 89.6）免疫的猕猴对 SHIVDH12 攻击具有更强的抵抗力（P = 0.039）。尽管不存在任何可检测到的NAb，但多价疫苗组中的动物（而非用Monovalent-89.6免疫的动物）表现出血浆病毒水平显着低于对照组的动物，这表明多价疫苗诱导的细胞介导的免疫反应优异。
The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus type 1 (HIV-l) isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. Most previously evaluated vaccine candidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of NAb and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from either single or multiple viral isolates. Animals were challenged with Simian/human immunodeficiency virus strain DH12 (SHTVDH12) following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (1) LAI, RIF, 89.6, ADS, and Bal (Polyvalent); (ii) LAI, RF, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6); and (iv) DH12 (Monovalent-DH12). Animals in the two polyvalent vaccine groups developed NAbs against more HIV-1 isolates than those in the two monovalent vaccine groups (P = 0.0054). However, the increased breadth of response was directed almost entirely against the vaccine strains. Resistance to SHIVDH12 strongly correlated with the level of NAbs directed against the virus on the day of challenge (P = 0.0008). Accordingly, the animals in the Monovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to the SHIVDH12 challenge than the macaques immunized with preparations lacking a DH12 component (viz. Polyvalent and Monovalent-89.6) (P = 0.039). Despite the absence of any detectable NAb, animals in the Polyvalent vaccine group, but not those immunized with Monovalent-89.6, exhibited markedly lower levels of plasma virus than those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine.