Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids

Abstract

Glycoengineered bacteria have emerged as a costeffective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naıve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naıve 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 antigenspecific antibody discovery.

Biomaterial engineering strategies for B cell immunity modulations

“…275–278 The ability to capture GC B cell dynamics within this hydrogel system also enabled the in vitro screening of glycoconjugate vaccines and significantly accelerated the antigenicity evaluations as compared with the animal immunization-based approach. 279 A B-cell lymphoma in vitro model based on a similar strategy informed the design of a novel combination therapy to attenuate treatment resistance. 280 Hydrogel has also been incorporated into microfluidic devices to assess B cell responses against vaccines.…”