Innovative micro physiological systems for vaccine development

Abstract

Micro Physiological systems (MPS) are biomimetic platforms that reconstitute the complex architecture of human organs and tissues in vitro. MPSs have the capacity to improve clinical development pipelines as they address certain translational limitations that exist in other pre-clinical models by providing human-relevant microenvironments. These platforms have already demonstrated their potential in vaccine development, as several variations of MPSs have recently been published that provided results relevant to vaccine trials in humans. Previous MPSs include approximations of peripheral and lymphoid tissue in static platforms to study the innate and adaptive response to vaccination, as well as a lymphoid-follicle-on-chip under dynamic flow which produces antigen-specific antibodies to vaccination. Up-and-coming devices could be used to study the interplay between vaccine reactogenicity and innate immune stimulation, and thereby derisk vaccine targets by elucidating their inflammatory profiles prior to advancement to clinical trials.

Keywords: Micro physiological systems; biomimetic; immunogenicity; in vitro; pre-clinical; reactogenicity; translational; vaccine.

Figure 1.

The advantages and disadvantages of current preclinical models.

Figure 2.

An MPS with muscle fibers and a dynamic, endothelial-cell-lined blood flow compartment that recapitulates the innate immune response to vaccination: (1) the vaccine is introduced to the skeletal muscle compartment, (2) inflammatory mediators diffuse across the ECM into the blood compartment where they (3) stimulate the endothelial and immune cells and induce immune cell migration across the endothelial barrier.

Figure 3.

A publicly available database of molecular biomarkers and clinical symptoms produced in humans after vaccination could be used in an iterative process to improve vaccine testing in vitro. in silico predictions of reactogenicity from in vitro data could be validated with the database and used to improve candidates before advancement to clinical trials, thereby derisking the pipeline and reducing costs overall.