Anamnestic antibody response after viral challenge in monkeys immunized with dengue 2 recombinant fusion proteins

Anamnestic antibody response after viral challenge in monkeys immunized with dengue 2 recombinant fusion proteins
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DOI:
10.1007/s00705-008-0050-9
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发表时间:
2008-05-01
影响因子:
2.7
通讯作者:
Guzman, Maria G.
Guzman, Maria G.
中科院分区:
医学4区
文献类型:
--
作者:
Bernardo, Lidice;Hermida, Lisset;Guzman, Maria G.

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据报道,登革热 2 包膜结构域 III 重组融合蛋白 [(融合 (PD5) 和插入 (PD3) 变体)] 在非人灵长类动物中诱导功能性抗体和保护性免疫反应的适用性。然而,免疫后抗体反应的评估与病毒血症检测测量的保护数据并不相关。在这里,我们对用登革热 2 重组蛋白免疫的猴子进行病毒攻击后的记忆性免疫反应进行了表征,试图定义可用于疫苗研究的保护相关性。与对照动物相比,用 PD5 免疫的猴子(最受保护的群体)在攻击后表现出抗 DENV-2 IgM 反应较早增加。与 PD3 免疫的动物相比,PD5 免疫的动物的血凝抑制 (HAI) 抗体明显提前增加。受到完全保护的猴子表现出最早的 HAI 抗体反应。这些结果强调了记忆抗体反应对于支持保护数据的有用性。攻击后诱导早期 HAI 和 IgM 抗体反应表明对猴子的登革热病毒 (DENV) 感染具有保护作用,支持它们在疫苗研究中用作保护相关物。
The suitability of dengue 2 envelope domain III recombinant fusion proteins [(fusion (PD5) and insertion (PD3) variants)] for inducing functional antibodies and a protective immune response in nonhuman primates has been reported. However, the evaluation of the antibody response after immunization did not correlate with the protection data as measured by viremia detection. Here, we characterized the anamnestic immune response after viral challenge in monkeys immunized with the dengue 2 recombinant proteins in an attempt to define correlates of protection useful for vaccine studies. Monkeys immunized with PD5 (most protected group) exhibited an earlier increase in the anti-DENV-2 IgM response after challenge compared to control animals. Hemagglutination-inhibiting (HAI) antibodies were increased significantly earlier in PD5-immunized animals compared to those immunized with PD3. The fully protected monkeys showed the earliest HAI antibody response. These results underline the usefulness of the anamnestic antibody response for supporting protection data. The induction of an early HAI and IgM antibody response after challenge suggest a protective role against dengue virus (DENV) infection in monkeys, supporting their use as correlates of protection in vaccine studies.