Increased vaccine tolerability and protection via NF-κB modulation
Increased vaccine tolerability and protection via NF-κB modulation
复制标题
DOI：
10.1126/sciadv.aaz8700
复制
发表时间：
2020-09-01
期刊：
影响因子：
13.6
通讯作者：
Esser-Kahn, A. P.
中科院分区：
文献类型：
--
作者：
Moser, B. A.;Steinhardt, R. C.;Esser-Kahn, A. P.
改善佐剂反应是开发针对某些病原体(如艾滋病毒或登革热)的疫苗的一条很有希望的途径。佐剂开发中的一个挑战是调节炎症反应，这可能会导致额外的副作用，同时保持免疫激活和保护。目前还没有批准的佐剂能够独立调节炎症和保护。在这里，我们展示了一种方法来限制炎症，同时保留并经常增加保护性反应。为了实现这一目标，我们将部分选择性核因子kappa B(NF-kappa B)抑制剂与几种当前的佐剂相结合。由此产生的疫苗减少了全身炎症，增强了保护性反应。在流感挑战模型中，我们证明了这种方法增强了保护作用。这种方法在广泛的佐剂和抗原上进行了测试。我们预计，这些研究将导致一种替代疫苗配方设计的方法，这种方法可能被证明广泛适用于各种佐剂和疫苗。
Improving adjuvant responses is a promising pathway to develop vaccines against some pathogens (e.g., HIV or dengue). One challenge in adjuvant development is modulating the inflammatory response, which can cause excess side effects, while maintaining immune activation and protection. No approved adjuvants yet have the capability to independently modulate inflammation and protection. Here, we demonstrate a method to limit inflammation while retaining and often increasing the protective responses. To accomplish this goal, we combined a partial selective nuclear factor kappa B (NF-kappa B) inhibitor with several current adjuvants. The resulting vaccines reduce systemic inflammation and boost protective responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method was tested across a broad range of adjuvants and antigens. We anticipate these studies will lead to an alternative approach to vaccine formulation design that may prove broadly applicable to a wide range of adjuvants and vaccines.