In silico programming of degradable microparticles to hide and then reveal immunogenic payloads in vivo

The ability to deliver but hide immunogenic payloads and then reveal them at predetermined times could lead to autonomously boosting vaccine formulations or improved antigen-adjuvant vaccine designs. We used in silico modeling to determine the appropriate formulation and material properties for poly(lactic-co-glycolic) acid (PLGA) microparticles such that they would delay the in vitro"unmasking" of an ovalbumin-alum payload for precise and predetermined intervals. A preferred formulation was then tested in vivo. In vivo T cell proliferation data confirmed the presentation of antigen released through the programmed delayed burst while antibody subclass data demonstrated immunogenicity comparable to that observed with established multiple injection prime-boost regimens.