Lymph node follicle formation and vaccination responses reconstituted in vitro in a human Organ Chip

Candidate vaccines and immunotherapeutic drugs often fail in clinical trials as human lymph node (LN) physiology is not faithfully modeled in animal models or immune cell cultures. Here we describe a microfluidic Organ Chip culture device that supports self-assembly of human blood-derived B and T lymphocytes into three-dimensional (3D), germinal center-like lymphoid follicles (LFs) containing Activation-Induced Cytidine Deaminase (AID) expressing lymphocytes. These microengineered LFs support plasma cell differentiation upon activation with IL-4 and CD40 agonistic antibody (AB) or inactivated S. aureus Cowan I (SAC). Immunization of the human LN chip with a quadrivalent split virion influenza vaccine resulted in plasma cell formation, viral strain-specific anti-hemagglutinin immunoglobulin G (IgG) production, and a secreted cytokine profile that recapitulates serum responses of vaccinated humans. Thus, the human LN chip may provide a new tool to study human immune reactions, evaluate vaccine responses, and validate the efficacies and toxicities of immunotherapies in vitro.