Lymphoid‐Tissue‐on‐Chip Recapitulates Human Antibody Responses In Vitro

ABSTRACT Reliable modeling of human adaptive immune responses is a prerequisite to understand processes leading to vaccine‐induced protective immunization, to overcome the poor predictive value of non‐clinical in vivo and in vitro models and to drive informed decisions in vaccine development pipelines. Here, we present a centrifugal microfluidics‐based organ‐on‐chip approach to generate an organotypic high density lymphoid‐tissue‐on‐chip. The model enables long‐term culture of lymphoid tissue while preventing autoactivation and shows raised antigen‐specific antibody responses against influenza vaccines for up to 4 weeks on‐chip. Antibody response of different magnitude and quality could be induced both by direct antigen exposure as well as by recruitment of peripheral antigen‐presenting cells. The model represents an attractive approach to evaluate the impact of the mode of antigen delivery on adaptive immune responses. Beyond applications in vaccine development, the lymphoid‐tissue‐on‐chip provides a platform to study cellular interactions during homeostasis, immune responses, and drug treatment over several weeks.