Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids
Tyler D. Moeller, Shivem B. Shah, Kristine Lai, Natalia Lopez‐Barbosa, Primit Desai, Wei‐Yao Wang, Zhe Zhong, David Redmond, Ankur Singh, Matthew P. DeLisa
Abstract
High Resolution Image Download MS PowerPoint Slide Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naı̈ve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naı̈ve B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B cell receptor clustering, intracellular signaling, and somatic hypermutation. These responses depended on the relative immunogenicity of the conjugate and correlated with the humoral response in vivo. The occurrence of these mechanisms was exploited for the discovery of high-affinity antibodies against components of the conjugate on a time scale that was significantly shorter than for typical animal immunization-based workflows. Collectively, these findings highlight the potential of synthetic organoids for rapidly predicting conjugate vaccine efficacy as well as expediting antigen-specific antibody discovery.