Presenting on “From albumin hitchhiking to cell painting: Engineering mucosal vaccines with enhanced delivery, immune activation, and efficacy”.

Birttany Hartwell, PhD, assistant professor of biomedical engineering at the University of Minnesota, will speak on Thursday, January 22, 2026 at 10:00 am in Whitaker 218.

Abstract: To better combat infectious threats like HIV, 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 drug 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 that is shuttled across mucosal epithelium by binding the neonatal Fc receptor (FcRn) widely expressed on its surface. Exploiting this biology, we have developed mucosal vaccines that ‘hitchhike’ on albumin to deliver immune cargo across mucosal tissues to activate frontline mucosal immunity against infections like COVID, influenza, and HSV. ‘Amph-vaccines’, consisting of protein antigens modified with an albumin-binding amphiphile tail, exhibit increased uptake into mucosal tissues, driving GC B cell activation and significantly enhancing serum and mucosal antibody responses in mice over 100-1000-fold compared to unmodified protein antigen. Furthermore, in addition to their albumin hitchhiking behavior, amphiphile vaccines demonstrate a secondary mechanism 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 such as polymer linker length. In this talk, I will discuss how we are using albumin hitchhiking and cell painting as strategies to tune vaccine kinetics and multivalency, with an end goal of driving immune activation and protection against disease. We are investigating these amph-vaccine strategies across multiple disease settings, including new directions in cancer. In all, our results suggest that employing amph-vaccines to deliver antigen presents a promising and tunable strategy to promote mucosal immunity and enhance immune activation, with opportunities for immunoengineering in settings ranging from infectious disease to cancer.

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. 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. She 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).

In-person attendance is preferred. Registration is required to attend virtually.