Controlling vaccine kinetics using tannic acid for enhanced humoral immunity.

Despite the success of global vaccination campaigns, vaccine access in low-resource settings is an ongoing challenge. Subunit vaccines are a well-established and clinically scalable intervention, yet they have achieved limited success for poorly immunogenic antigens such as those associated with SARS-CoV-2. Delivery strategies that promote gradual release of subunit vaccines from the injection site offer the potential to improve humoral immunity by enhancing lymph node exposure, however, clinical implementation of this strategy is challenging due to poor scalability and high costs. Here, we propose an approach that uses the polyphenol tannic acid (TA) as a simple and inexpensive strategy to enhance tissue residence of vaccines and subsequent humoral immunity. We show that TA mediates supramolecular interactions between vaccine components and tissue at the subcutaneous injection site to promote extended retention of protein antigens for over one week. In addition to enhancing the magnitude and duration of vaccine drainage to the lymph nodes, inclusion of TA improved accumulation of activated, antigen-laden monocyte-derived dendritic cells (moDCs), promoting long-lasting humoral immunity against the receptor-binding domain (RBD) of SARS-CoV-2 and variants of concern. This system, termed TAPER (Tannic Acid-Promoted Enhanced Retention) provides various translational advantages including one-pot synthesis, scalability, low cost, and modularity, towards realization of effective and accessible subunit vaccines.