The current paradigm that subunit vaccines require adjuvants to optimally activate innate immunity implies that increased vaccine reactogenicity will invariably be linked to improved immunogenicity. Countering this paradigm, nanoparticulate vaccines have been reported to act as delivery systems for vaccine antigens and induce immunity without the need for exogenous adjuvants or local inflammation; however, the mechanisms underlying the immunogenicity of nanoparticle vaccines are incompletely identified. Here, we show that antigens displayed on self-assembling nanofiber scaffolds and delivered intranasally are presented by CD103+ and CD11b+ lung dendritic cells that up-regulate CD80 and migrate into the draining lymph node (LN). This was accompanied by a nearly exclusive priming and accumulation of antigen-specific TH17 cells occurring independently in both LN and lung. Thus, self-assembling peptide nanofiber vaccines may represent a novel, needle- and adjuvant-free means of eliciting protective immunity against fungal and bacterial infections at skin and mucosal barrier surfaces.

No abstract

No abstract

No abstract

Obese subjects have increase probabilities of developing type 2 diabetes (T2D). In this study, we sought to determine whether gastric bypass prevents the progression of prediabetes to overt diabetes in genetically modified mice and chemically induced diabetic mice. Roux-en-Y gastric bypass (RYGB) was performed in C57BL/KsJ-db/db null (BKS-db/db,) mice, high-fat diet (HFD)-fed NONcNZO10/LtJ (NZO) mice, C57BL/6 db/db null (B6-db/db) mice and streptozotocin (STZ)-induced diabetic mice. Food consumption, body weight, fat mass, fast blood glucose level, circulating insulin and adiponectin and glucose tolerance test were analyzed. The liver and pancreatic tissues were subjected to H&E and immunohistochemistry staining and islet cells to flow cytometry for apoptotic analysis. RYGB resulted in sustained normoglycemia and improved glucose tolerance in young prediabetic BKS-db/db mice (at the age of 6 weeks with hyperglycemia and normal insulinemia) and HFD-fed NZO and B6-db/db mice. Remarkably, RYGB improved liver steatosis, preserved the pancreatic β-cells and reduced β-cell apoptosis with increases in circulating insulin and adiponectin in young prediabetic BKS-db/db mice. However, RYGB neither reversed hyperglycemia in adult diabetic BKS-db/db mice (12 weeks old) nor attenuated hyperglycemia in STZ-induced diabetic mice. These results demonstrate that gastric bypass improves hyperglycemia in genetically modified prediabetic mice; however, it should be performed prior to β-cells exhaustion.