Optimization of Prime-Boost Vaccination Strategies Against Mouse-Adapted Ebolavirus in a Short-Term Protection Study
Optimization of Prime-Boost Vaccination Strategies Against Mouse-Adapted Ebolavirus in a Short-Term Protection Study
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DOI：
10.1093/infdis/jiv175
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发表时间：
2015-10-01
影响因子：
6.4
通讯作者：
Kobinger, Gary
中科院分区：
文献类型：
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作者：
Aviles, Jenna;Bello, Alexander;Kobinger, Gary
在非人类灵长类动物中，以前在单次注射几种疫苗平台后实现了对埃博拉病毒（EBOV）挑战的完全保护。然而，迄今尚未证明单次免疫接种后对EBOV具有长期保护作用。有趣的是，与单一免疫相比，预强化方案对EBOV的保护作用更长。由于初始强化方案有可能实现长期保护，因此确定最佳载体组合至关重要。然而，在长期保护研究中测试初始增强效率是耗时和资源需求的。在此，我们利用DNA、猪源性腺相关病毒血清6型（AAV-po6）和人腺病毒血清5型（Ad5）载体，对EBOV感染小鼠模型进行了短期保护研究，研究了最佳的启动-增强组合。此外，我们还研究了哪些免疫参数表明有很强的促进作用。在小鼠中对每种疫苗平台进行滴定，以确定哪种剂量（单次免疫）在小鼠适应的EBOV攻击后诱导约20%的保护。然后使用相同的小鼠模型，使用这些剂量来确定各种初始-增强组合的保护效果。此外，通过酶联免疫吸附试验、中和抗体试验和干扰素分析体液和细胞对EBOV糖蛋白的免疫反应。-特异性酶联免疫斑点试验。当DNA被用作引物时，Ad5增强诱导了最好的保护，这与更高的细胞反应相关。相比之下，当先注射AAV-po6或Ad5时，DNA增强后的保护效果更好，这与更高的总糖蛋白特异性免疫球蛋白G滴度相关。使用独立疫苗平台的启动-增强方案可能提供一种有用的策略，以诱导对丝状病毒的长期免疫保护。
In nonhuman primates, complete protection against an Ebola virus (EBOV) challenge has previously been achieved after a single injection with several vaccine platforms. However, long-term protection against EBOV after a single immunization has not been demonstrated to this date. Interestingly, prime-boost regimens have demonstrated longer protection against EBOV challenge, compared with single immunizations. Since prime-boost regimens have the potential to achieve long-term protection, determining optimal vector combinations is crucial. However, testing prime-boost efficiency in long-term protection studies is time consuming and resource demanding. Here, we investigated the optimal prime-boost combination, using DNA, porcine-derived adeno-associated virus serotype 6 (AAV-po6), and human adenovirus serotype 5 (Ad5) vector, in a short-term protection study in the mouse model of EBOV infection. In addition, we also investigated which immune parameters were indicative of a strong boost. Each vaccine platform was titrated in mice to identify which dose (single immunization) induced approximately 20% protection after challenge with a mouse-adapted EBOV. These doses were then used to determine the protection efficacy of various prime-boost combinations, using the same mouse model. In addition, humoral and cellular immune responses against EBOV glycoprotein were analyzed by an enzyme-linked immunosorbent assay, a neutralizing antibody assay, and an interferon.-specific enzyme-linked immunospot assay. When DNA was used as a prime, Ad5 boost induced the best protection, which correlated with a higher cellular response. In contrast, when AAV-po6 or Ad5 were injected first, better protection was achieved after DNA boost, and this correlated with a higher total glycoprotein-specific immunoglobulin G titer. Prime-boost regimens using independent vaccine platforms may provide a useful strategy to induce long-term immune protection against filoviruses.