MEMP PhD Thesis Defense (11:00am): Morgan Janes

Engineering translational vaccine delivery systems with the polyphenol tannic acid

Supramolecular biomaterials, which are capable of spontaneous assembly via diverse non-covalent interactions, represent an exciting frontier in drug delivery due to their ease of formulation and modularity. Tannic acid (TA) is a naturally occurring polyphenol that has a demonstrated ability to engage in supramolecular interactions with biological cargo, including proteins, nucleic acids, and cell membranes. In this thesis, I harness the broad bio-adhesive capacity of TA to develop scalable, modular systems for vaccine engineering that span various modalities and applications.

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 weak or rapidly evolving antigens such as those associated with SARS-CoV-2. Delivery strategies that promote gradual release of subunit vaccines from the site of injection may improve humoral immunity by enhancing the duration of lymph node exposure, however, clinical implementation of this approach is challenging due to poor scalability and high costs.

Here, we use TA to engineer adhesive vaccine formulations as a simple and inexpensive strategy to enhance subunit vaccine immunogenicity. We show that TA mediates deposition and retention of protein antigens at the subcutaneous injection site for over one week. In addition to enhancing the magnitude and duration of vaccine drainage to the lymph nodes, inclusion of TA induces lymph node accumulation of antigen-laden monocyte-derived dendritic cells (moDCs), eliciting durable antibody titers against the receptor-binding domain (RBD) of SARS-CoV-2 and variants of concern in mice. The benefits of supramolecular vaccine formulations containing TA, such as one-pot synthesis, scalability, low cost, and modularity, open the door for the realization of effective and clinically feasible subunit vaccination strategies.

Thesis Supervisor:
Samir Mitragotri, PhD
Hiller Professor of Bioengineering, Harvard University, Hansjorg Wyss Professor of Biologically Inspired Engineering, Wyss Institute

Thesis Committee Chair:
Darrell Irvine, PhD
Professor of Biological Engineering and Materials Science & Engineering, MIT

Thesis Reader:
David Avigan, MD
Professor of Medicine, Harvard Medical School, Chief of Division of Hematology/Hematologic Malignancy, Beth Israel Deaconess Medical Center
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Morgan Elizabeth Janes is inviting you to a scheduled Zoom meeting.

Topic: Morgan Janes Thesis Defense
Time: Mar 1, 2024, 11:00 AM Eastern Time (US and Canada) 

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