Biodegradable Microparticles Coated with Lipid-like Immunostimulatory Molecules Elicit Rapid and Lasting Antibody Responses to Modest Antigen Doses.

摘要

We have created a vaccine delivery platform based on biodegradable polymer particles enveloped by a lipid shell. Using lipid as the sole surfactant in emulsion synthesis of the particles leads to self-assembly of a stable, two-dimensionally fluid bilayer surface. The bilayer supports spontaneous incorporation of biologically relevant lipid-like molecules, including several vaccine adjuvants. Incorporation of functionalized lipids allows covalent coupling of protein to particle surfaces at neutral pH. Natural killer T cell agonist a-galactosylceramide provided more rapid antibody responses to modest doses when co-delivered with antigen, whereas Toll-like receptor 4 agonist monophosphoryl lipid A provided longer-lasting immunity at 100-fold lower antigen doses.