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ABSTRACT Formation of alginate‐based interpenetrating networks and addition of nanoparticles into these gels are widely used strategies to enhance the mechanical properties of alginate gels used for delivery and biomedical applications. Our previous work demonstrated that alginate‐clay nanocomposite hydrogels containing poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) copolymers exhibited significant enhancement of elasticity and temperature‐dependent rheology. However, the behavior of PEO–PPO–PEO copolymers within an alginate network remains unclear. In this study, we use small‐angle neutron scattering (SANS) to investigate the interactions between the alginate network and PEO–PPO–PEO triblock chains. Our fitting results revealed that the triblock chains can form micelles integrated into the alginate gel “egg box” structure at higher temperatures. The presence of the alginate network influences the formation of PEO–PPO–PEO micelles in our gels, leading to elongated ellipsoidal micelles rather than spherical micelles. Interestingly, as the temperature increased, these micelles did not expand in all three dimensions, as observed for pure PEO–PPO–PEO solutions. Rather, the total size increased only in one direction while remaining the same in the other two directions, suggesting that the alginate networks restrict the growth of micelles. Furthermore, we did not observe the distinct higher‐order peaks that are typical of cubic PEO–PPO–PEO hydrogels; rather, relatively weak secondary peaks were observed. These results demonstrate that the presence of the alginate network significantly influences micelle formation and assembly in composite hydrogel systems. 

ABSTRACT The development of vaccines for fungal diseases, including cryptococcosis, is an emergent line of research and development. In previous studies, we showed that aCryptococcusmutant lacking theSGL1gene (∆sgl1) accumulates certain glycolipids called steryl glucosides (SGs) on the fungal capsule, promoting an effective immunostimulation that totally protects the host from a secondary cryptococcal infection. However, this protection is lost when the cryptococcal capsule is absent in the∆sgl1background. The cryptococcal capsule is mainly composed of glucuronoxylomannan (GXM), a polysaccharide microfiber consisting of glucuronic acid, xylose, and mannose linked by glycosidic bonds forming specific triads. In this study, we engineered cells to lack each of the GXM components and tested the effect of these deletions on protection under the condition of SG accumulation. We found that glucuronic acid and xylose are required for protection, and their absence abrogates the production of IFNγ and IL-17A by γδ T cells, which are necessary stimulants for the protective phenotype of the∆sgl1. We analyzed the structure of the GXM microfibers and found that although the deletion ofSGL1only slightly affects the size and distribution of these microfibers, it significantly changes the ratio of mannose to other components. In conclusion, this study identifies the structural modifications that the deletion ofSGL1and the consequent accumulation of SGs impart to the GXM structure ofC. neoformans. This provides significant insights into the protective mechanisms mediated by SG accumulation on the capsule, with important implications for the future development of an efficacious cryptococcal vaccine.IMPORTANCECryptococcus neoformansis an encapsulated fungus that causes invasive fungal infections with high morbidity and mortality in susceptible patients. With increasing drug resistance and high toxicity of current antifungal drugs, there is a need for alternative therapeutic strategies, such as a cryptococcal vaccine. In this study, we identify the necessary capsular components and their structural organization required for a cryptococcal vaccine to protect the host against challenge with a virulent strain. These capsular components are glucuronic acid, xylose, and mannose, and they work together with certain glycolipids called steryl glucosides (SGs) to stimulate host immunity. Interestingly, SGs on the capsule may favor the formation of small capsular microfibers organized in specific mannose triads. Thus, the results of this paper are important because they identify a mechanism by which SGs affect the structure of the cryptococcal capsule, with important implications for the future development of a cryptococcal vaccine using capsular components and SGs. 

Vaccines are a pivotal achievement in public health, offering inexpensive, distributable and highly effective protection against infectious diseases. Despite significant advancements in vaccine development, there are still many diseases for which vaccines are unavailable or offer limited protection. The global impact of the deficiency in vaccine‐induced immunity against these diseases is profound, leading to increased rates of illness, more frequent hospitalizations, and higher mortality rates. Recent studies have demonstrated conjugation mechanisms and delivery methods to co‐present adjuvants and protein epitopes to antigen‐presenting cells, significantly enhancing adaptive immunity. We introduce a novel approach to incorporate an adjuvant into the vaccine by covalently attaching it to whole enveloped virions. Using clickable azide‐enabled viral particles, generated through metabolic incorporation of N‐azidoacetyl glucosamine (GlcNAz), we conjugated the virions with a cyclo‐octyne‐modified CpG‐ODN. Conjugation yielded a potent adjuvant‐virus complex, eliciting higher TLR9‐mediated cell activation of cultured bone marrow‐derived macrophages relative to co‐administered adjuvants and virions. Administration of covalent adjuvant‐virion conjugates increase immune cell stimulation and may provide a generalizable and effective strategy for eliciting a heightened immune response for vaccine development. 

Abstract We report the thermoresponsive assembly and rheology of an amphiphilic thermosensitive graft copolymer, poly(ethylene glycol)-graft-(poly(vinyl caprolactam)- co -poly(vinyl acetate)) (commercial name Soluplus ® ), which has been investigated for potential biomedical applications. It has received attention due to is ability to solubilize hydrophobic drugs and for its thickening behavior close to body temperature. Through use of the synchrotron at Brookhaven National Lab, and collaboration with the department of energy, the nanoscale structure and properties can be probed in greater detail. Soluplus ® undergoes two structural changes as temperature is increased; the first, a concentration independent change where samples become turbid at 32 °C. Increasing the temperature further causes the formation of physically associated hydrogels. This sol-gel transition is concentration dependent and occurs at 32 °C for 40 wt% samples, and increases to 42 °C for 10 wt% samples. From variable temperature SAXS characterization micelles of 20–25 nm in radius can be seen and maintain their size and packing below 32 °C. A gradual increase in the aggregation of micelles corresponding to a thickening of the material is also observed. Close to and above the gelation temperature, micelles collapse and form a physically associated 3D network. A model is proposed to explain these physical effects, where the poly(vinyl caprolactam) group transitions from the hydrophilic corona at room temperature to the hydrophobic core as temperature is increased.