title: Shape and size-dependent immune response to antigen-carrying nanoparticles.
abstract: The immune system has evolved to recognize and respond to a wide variety of pathogens and produce distinct immune responses against diverse pathogenic structures. Despite remarkable advances, the general mechanisms by which the immune system differentiates the structure of antigen presenting particulates have yet to be elucidated. Using particles of various sizes and shapes, we assessed the role of morphological features of particles in antigen presentation and subsequent processing by the immune cells. Ovalbumin was used as a model antigen. Spherical polystyrene particles of 193 nm and 521 nm diameters were successfully stretched to form rod-shaped particles of 376 nm and 1530 nm in length, respectively. Ovalbumin conjugation to these different particle types was optimized to achieve ~50 μg of ovalbumin conjugation per mg of particle. In vivo immunization study results revealed that small spherical particles (193 nm in diameter) produced a Th1-biased response whereas rod-shaped particles (1530 nm in length) produced a Th2-biased response against ovalbumin. Among different particle types, smaller spherical (193 nm) particles generated stronger Th1 and Th2 immune responses compared to the other particle types. In vitro studies with dendritic cells indicated that spherical (193 nm) and rod (1530 nm) shaped particles were internalized by dendritic cells and delivered ovalbumin. These results provide evidence for size- and shape-dependent modulation of immune responses and this knowledge can be leveraged to rationally design and develop next generation vaccines against a wide range of pathogens.
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Amrita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Zakrewsky
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States. Electronic address: samir@engineering.ucsb.edu.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000276:immunology*; D010316:Particle Size; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D010047:Ovalbumin
keywords: Antigen; Immune response; Morphology; Nanoparticles; Shape; Size; Vaccine