Vaccine efficacy can be increased by arraying immunogens in multivalent form on virus-like nanoparticles to enhance B cell activation. However, the effects of antigen copy number, spacing, and affinity, as well as the dimensionality and rigidity of scaffold presentation on B cell activation remain poorly understood. Here, we displayed the clinical vaccine immunogen eOD-GT8, an engineered outer domain of the HIV-1 glycoprotein-120, on DNA origami nanoparticles to systematically interrogate the impact of these nanoscale parameters on B cell activation in vitro. We found that B cell signalling is maximized by as few as five antigens maximally spaced on the surface of a 40 nm viral-like nanoparticle. Increasing antigen spacing up to ~25–30 nm monotonically increases B cell receptor activation. Moreover, scaffold rigidity is essential for robust B cell triggering. These results reveal molecular vaccine design principles that may be used to drive functional B cell responses.

No abstract

Self-assembling peptide amphiphile (PA) nanofibers were used to encapsulate camptothecin (CPT), a naturally occurring hydrophobic chemotherapy agent, using a solvent evaporation technique. Encapsulation by PA nanofibers was found to improve the aqueous solubility of the CPT molecule by more than 50-fold. PAs self-assembled into nanofibers in the presence of CPT as demonstrated by transmission electron microscopy. Small-angle X-ray scattering results suggest a slight increase in diameter of the nanofiber to accommodate the hydrophobic cargo. In vitro studies using human breast cancer cells show an enhancement in antitumor activity of the CPT when encapsulated by the PA nanofibers. In addition, using a mouse orthotopic model of human breast cancer, treatment with PA nanofiber encapsulated CPT inhibited tumor growth. These results highlight the potential of this model PA system to be adapted for delivery of hydrophobic therapies to treat a variety of diseases including cancer.

No abstract