基于蛋白质的疫苗为减毒活疫苗或灭活疫苗提供了更安全的替代品,但免疫原性有限。增强免疫原性的佐剂的鉴定,特别是以持久和抗原特异性的方式,因此对先进发展至关重要。在这项研究中,我们使用丝状病毒病毒样颗粒(VLP)作为基于蛋白质的模型疫苗,以评估4种候选疫苗佐剂对增强对埃博拉病毒攻击的长期保护作用的影响.测试的佐剂包括聚-ICLC(希尔顿诺),MPLA,CpG2395和alhydrogel。我们比较和对比了抗体反应,中和抗体反应,效应T细胞反应,和T滤泡辅助(Tfh)细胞频率与每种佐剂对持久保护的影响。我们证明在这个系统中,最有效的佐剂引发Th1偏斜的抗体反应和强烈的CD4T细胞反应,包括Tfh频率的增加。使用免疫缺陷的动物和过继转移的血清和细胞从接种疫苗的动物到幼稚的动物,我们进一步证明,在有效的疫苗接种方案中,血清和CD4T细胞在赋予保护作用方面发挥着关键作用.这些研究提供了长期免疫保护的要求,可用于指导临床级佐剂的筛选,用于疫苗临床开发。
Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant\'s impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.