Event
BIOE Seminar: Engineering mucosal vaccines with enhanced delivery and efficacy
Friday, September 25, 2026
9:00 a.m.
A. James Clark Hall, Room #2121
Rohan Fernandes
rohan@umd.edu
Brittany Hartwell
Assistant Professor
University of Minnesota
From albumin hitchhiking to cell painting: Engineering mucosal vaccines with enhanced delivery and efficacy
Abstract
To better combat infectious threats from HIV to SARS-CoV-2 and influenza, immunization strategies are needed that trigger immune protection in mucosal portals of pathogen entry. While traditional injected vaccines are effective at activating ‘backup’ immune defenses in the blood, they typically do not activate robust ‘frontline’ defenses in mucosal tissues where transmission takes place. Vaccinating directly at mucosal surfaces (for example, through the nose) can promote mucosal immunity by initiating local immune activation in underlying mucosal associated lymphoid tissues. In particular, activating germinal center (GC) responses in lymphoid tissues is an important target for many infectious disease vaccines, as GCs serve as the training ground for B cells and a protective antibody response. However, development of mucosal subunit vaccines has been largely hindered by challenges of drug delivery across mucosal barriers and poor vaccine uptake into these key centers of immune activation. Thus, our lab is developing engineering strategies for molecular subunit vaccines to both (1) enhance delivery across mucosal barriers to underlying lymphoid tissues, and (2) more effectively activate pivotal immune cells like B cells once there. One such strategy takes advantage of a naturally occurring serum protein, albumin, found in blood and mucosal fluids. Albumin is shuttled across mucosal barriers by binding the neonatal Fc receptor (FcRn) widely expressed on mucosal epithelial cells. By modifying vaccine components (antigens, adjuvants) with an albumin-binding amphiphile tail, we have developed intranasal vaccines that ‘hitchhike’ on albumin to deliver immune cargo across mucosal barrier tissues to activate frontline immunity in the nose, lungs, and genitourinary tract. With this modification, ‘amph-protein’ conjugate vaccines significantly enhance serum and mucosal antibody responses in mice over 1000-fold compared to unmodified protein antigen. In addition to their albumin hitchhiking behavior, amph-protein vaccines demonstrate a secondary behavior of ‘cell painting’ in which the amphiphile tail inserts into cell membranes to effectively ‘paint’ cells with multivalent antigen. Our work demonstrates that cell painting enhances vaccine immunogenicity through multivalent B cell activation and GC priming, a behavior that can be tuned by modulating physicochemical properties of the amphiphile platform like polymer linker length. In this talk, I will discuss how we are using both albumin hitchhiking and cell painting as strategies to tune vaccine delivery, kinetics, and immune activation potential, with an end goal of driving immune activation for protection against disease.
Bio
Dr. Brittany Hartwell is an Assistant Professor of Biomedical Engineering at the University of Minnesota. Her lab’s research in immunoengineering combines perspectives from biomolecular engineering, drug delivery, and immunology to develop molecular platforms that can target specific cells and tissues of the immune system to direct the immune response, with a particular focus on targeting and 'tuning’ mucosal immunity. This work has broad applications ranging from the development of antigen-specific immunotherapies that induce immune tolerance against autoimmune and chronic inflammatory diseases, to development of targeted vaccines that activate immune protection against cancer and infectious diseases. For this work she was selected as one of four researchers worldwide to receive a 2022 Michelson Prize, awarded to early career investigators in human immunology and vaccine research. She also received a PhRMA Foundation Faculty Starter Grant in Drug Delivery in 2025. Prior to starting her faculty position at the University of Minnesota in fall 2021, she completed postdoctoral training with Dr. Darrell Irvine at Massachusetts Institute of Technology (2021) in immunoengineering, where she worked on developing targeted mucosal vaccines against HIV and COVID. Hartwell received her PhD in biomolecular engineering with Dr. Cory Berkland at the University of Kansas (2016), where she worked on developing multivalent antigen-specific immunotherapy platforms for autoimmune diseases like multiple sclerosis. She received her B.S. in chemical and biological engineering from Iowa State University (2011).
