Sustained Delivery of CpG Oligodeoxynucleotide by Acetalated Dextran Microparticles Augments Effector Response to Computationally Optimized Broadly Reactive Antigen (COBRA) Influenza Hemagglutinin.

Nanomedicine is a new discipline resulting from the combination of nanotechnology and biomedicine. Nanomedicine has contributed to the development of new and improved treatments, diagnoses, and therapies. In this field, nanoparticles have notable importance due to their unique properties and characteristics, which are useful in different applications, including tissue engineering, biomarkers, and drug delivery systems. Electrospinning is a versatile technique used to produce fibrous mats. The high surface area of the electrospun mats makes them suitable for applications in fields using nanoparticles. Electrospun mats are used for tissue engineering, wound dressing, water-treatment filters, biosensors, nanocomposites, medical implants, protective clothing materials, cosmetics, and drug delivery systems. The combination of nanoparticles with nanofibers creates hybrid systems that acquire properties that differ from their components’ characteristics. By utilizing nanoparticles and nanofibers composed of dissimilar polymers, the two synergize to improve the overall performance of electrospinning mats and nanoparticles. This review summarizes the hybrid systems of polymeric nanoparticles and polymeric nanofibers, critically analyzing how the combination improves the properties of the materials and contributes to the reduction of some disadvantages found in nanometric devices and systems.

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Hybrid Systems of Nanofibers and Polymeric Nanoparticles for Biological Application and Delivery Systems

Influenza is a global health concern with millions of infections occurring yearly. Seasonal flu vaccines are one way to combat this virus; however, they are poorly protective against influenza as the virus is constantly mutating, particularly at the immunodominant hemagglutinin (HA) head group. A more broadly acting approach involves Computationally Optimized Broadly Reactive Antigen (COBRA). COBRA HA generates a broad immune response that is capable of protecting against mutating strains. Unfortunately, protein-based vaccines are often weekly immunogenic, so to help boost the immune response, we employed the use of acetalated dextran (Ace-DEX) microparticles (MPs) two ways: one to conjugate COBRA HA to the surface and a second to encapsulate cGAMP. To conjugate the COBRA HA to the surface of the Ace-DEX MPs, a poly(L-lactide)-polyethylene glycol co-polymer with a vinyl sulfone terminal group (PLLA-PEG-VS) was used. MPs encapsulating the STING agonist cGAMP were co-delivered with the antigen to form a broadly active influenza vaccine. This vaccine approach was evaluated in vivo with a prime-boost-boost vaccination schedule and illustrated generation of a humoral and cellular response that could protect against a lethal challenge of A/California/07/2009 in BALB/c mice. Graphical Abstract

Jonathan Williams

Papers

Multiplexed Electrospray Enables High Throughput Production of cGAMP Microparticles to Serve as an Adjuvant for a Broadly Acting Influenza Vaccine.