Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity.

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility. Peptide amphiphile micelles have recently been shown to function as both delivery devices and self-adjuvanting systems that can be readily associated with molecular adjuvants to further improve vaccine-mediated host immunity. While promising, many "design rules" associated with the plethora of underlying adjustable parameters in the generation of a peptide amphiphile micelle vaccine have yet to be uncovered. This work explores the impact micellar adjuvant complexation method and incorporated antigen type have on their ability to activate dendritic cells and induce antigen specific responses. Interestingly, electrostatic complexation of CpG to micelles resulted in improved in vitro dendritic cell activation over hydrophobic association and antigen|adjuvant co-localization influenced cell-mediated, but not antibody-mediated immune responses. These exciting results complement those previously published to build the framework of a micelle vaccine toolbox that can be leveraged for future disease-specific formulations.

Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection.

Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.