Carl N. Urbani

Polyacrylate Dendrimer Nanoparticles: A Self‐Adjuvanting Vaccine Delivery System

(Figure Presented) Special delivery: An effective group A streptococci vaccine is formed from a delivery device consisting of well-defined dendritic structures with nanoscale dimensions (see picture). The structures are designed to display multiple copies of the minimal B-cell epitopes, which were in the optimal conformation on the surface of the nanoparticles. The nanoparticles can be administered without the aid of an adjuvant.

Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine

UNLABELLED Infection with Streptococcus pyogenes, commonly known as group A Streptococcus (GAS), is responsible for acute and postinfectious complications, including rheumatic fever and rheumatic heart disease (RHD). RHD is a global health burden, and Australias indigenous population has one of the highest incidences of RHD worldwide. A potential peptide (J14) vaccine candidate has been previously identified from the C-terminal region of the M protein. However, such peptide-based vaccine development is hampered by a lack of carriers and adjuvants suitable for humans use. We have developed a fully synthetic peptide subunit vaccine candidate based on polyacrylate dendritic polymer. Intranasal administration of this nanoparticulate construct without additional adjuvant induced J14-specific IgG, which was also capable of in vitro opsonization of GAS, highlighting the potential of self-adjuvanting polyacrylate nanoparticle-based construct as a peptide vaccine delivery platform that may afford promising opportunities for treating systemic GAS infection. FROM THE CLINICAL EDITOR Polyacrylate dendrimers offer a unique approach to a nasally administered vaccine for addressing rheumatic heart disease. This paper describes the delivery of the J14 peptide, a C-terminal derivative of M-protein in group A Streptococcus.

Mechanically driven reorganization of thermoresponsive diblock copolymer assemblies in water

Controlled formation of a variety of 3D structures was observed at high polymer weight fractions in water from a single diblock, consisting of poly(N-isopropylacrylamide), PNIPAM, and polystyrene, PSTY segments. The structures form through a mechanical process driven by swelling of hydrophilic polymer segments upon a change in temperature.

RAFT-Mediated Emulsion Polymerization of Styrene in Water using a Reactive Polymer Nanoreactor

We have demonstrated a nanoreactor methodology to produce polystyrene nanoparticles with narrow molecular weight distributions (MWD) and control over the final particle size distributions. Our reactive thermoresponsive diblock copolymer nanoreactor is an ideal setting to carry out otherwise difficult reversible addition-fragmentation chain transfer (RAFT)mediated polymerizations, resulting in surfactant-free nanoparticles that can be tuned to size and MWD. By confining the MacroRAFT agent within the nanoreactor, the poor P(DMA(68)-b-NIPAM(73))-SC(=S)SC4H9 (PNIPAM) leaving group on the MacroCTA behaves as a highly active MacroCTA through kinetic rather than thermodynamic control. The M-n was close to theory with low polydispersity indices (PDIs)(<1.2). The particle size increased with the ratio of styrene to nanoreactors and with very narrow particle size distributions. However, we found that there was a limited amount of styrene monomer that can be encapsulated into the nanoreactor, leading to polymerizations stopping well before full conversion. This problem was overcome through the addition of a non-reactive thermoresponsive diblock copolymer, which resulted in M(n)s close to 340 K and low PDIs.