Development of a nanoparticle-based influenza vaccine using the PRINT® technology

Abstract

Historically it is known that presentation of vaccine antigens in particulate form, for a wide range of pathogens, has clear advantages over the presentation of soluble antigen alone [J.C. Aguilar, E.G. Rodriguez, Vaccine adjuvants revisited. Vaccine 25 (2007) 3752–3762, M. Singh, D. O'Hagan, Advances in vaccine adjuvants. Nature Biotechnology 17 (1999) 1075–1081]. Herein we describe a novel particle-based approach, which independently controls size, shape, and composition to control the delivery and presentation of vaccine antigen to the immune system. Highly uniform particles were produced using a particle molding technology called PRINT® (Particle Replication in Non-wetting Templates) which is an off-shoot of imprint lithography [J Am Chem Soc 127 (2005) 10096–10100, J Am Chem Soc 126 (2004) 2322–2323, Chem Soc Rev 35 (2006) 1095–1104, J Am Chem Soc 130 (2008) 5008–5009, J Am Chem Soc 130 (2008) 5438–5439, Polymer Reviews 47 (2007) 321–327, Acc Chem Res 41 (2008) 1685–1695, Acc Chem Res 44 (10) (2011) 990–998]. Cylindrical (diameter [d]=80nm, height [h]=320nm) poly (lactide-co-glycolide) (PLGA) based PRINT particles were designed to electrostatically bind commercial trivalent injectable influenza vaccine. In a variety of blended PLGA formulations, these particles were safe and showed enhanced responses to influenza hemagglutinin in murine models. From the Clinical EditorShape is one of the determining factors in interactions of nanoparticles with their biologic environment. PRINT technology is able to fabricate nearly uniform nanoparticles and this technology is tested here in murine models to effectively deliver influenza vaccine.