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

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.