Prime-Boost Immunization Strategies against Chikungunya Virus
Prime-Boost Immunization Strategies against Chikungunya Virus
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DOI：
10.1128/jvi.01926-14
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发表时间：
2014-11-01
影响因子：
5.4
通讯作者：
Liljestrom, Peter
中科院分区：
文献类型：
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作者：
Hallengard, David;Lum, Fok-Moon;Liljestrom, Peter
基孔肯雅病毒（CHIKV）是一种再次出现的蚊媒甲病毒，可导致人类关节痛衰弱。在这里，我们描述了新的DNA复制子和蛋白质候选疫苗的开发和测试，并评估了它们诱导针对CHIKV的抗原特异性免疫反应的能力。我们还描述了使用新型和先前开发的CHIKV候选疫苗的同源和异源启动-增强免疫策略。在小鼠CHIKV感染模型中研究了免疫原性和有效性，结果表明DNA复制子和蛋白质抗原是有效的候选疫苗，特别是分别用于引物和增强时。确定了几种启动-增强免疫策略，可引起无与伦比的体液和细胞免疫反应。抗体表位定位的进一步表征揭示了不同候选疫苗和免疫策略诱导的定性免疫反应的差异。大多数疫苗形式都能完全预防野生型CHIKV感染；然而，我们确实确定了某些免疫方案可能导致炎症增强的情况。这些结果应有助于指导CHIKV疫苗研究的设计，并将为进一步对这些候选疫苗进行临床前和临床评价奠定基础。到目前为止，还没有获得许可的疫苗来预防CHIKV感染。在考虑潜在的新候选疫苗时，一种能够在单次免疫后提高长期保护性免疫的疫苗将是可取的。虽然体液免疫似乎是防止CHIKV感染的核心保护，但我们尚未完全了解保护的相关性。因此，在缺乏功能性疫苗的情况下，有必要评估许多不同的候选疫苗，评估它们在单次免疫或同源或异源启动-增强模式中使用时的优点。本研究表明，虽然使用多种候选疫苗进行单一免疫可产生有效的应答，但联合方法可显著增强应答，这表明在进一步开发有效的CHIKV疫苗时需要考虑这种方法。
Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates.IMPORTANCEAs of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.