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-kB) 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.

改善佐剂反应是开发针对某些病原体（例如艾滋病毒或登革热）的疫苗的一条有前途的途径。佐剂开发的一项挑战是调节炎症反应，这可能会导致过度的副作用，同时保持免疫激活和保护。目前还没有批准的佐剂具有独立调节炎症和保护的能力。在这里，我们展示了一种限制炎症的方法，同时保留并经常增强保护反应。为了实现这一目标，我们将部分选择性核因子 kappa B (NF-kB) 抑制剂与几种现有佐剂结合起来。由此产生的疫苗可以减少全身炎症并增强保护反应。在流感挑战模型中，我们证明这种方法可以增强保护。该方法在多种佐剂和抗原上进行了测试。我们预计这些研究将带来疫苗配方设计的替代方法，该方法可能广泛适用于各种佐剂和疫苗。