Peptide Glycodendrimers as Potential Vaccines for Olive Pollen Allergy.
Sara BenedéJavier Ramos-SorianoFrancis PalomaresJorge LosadaAinhoa MascaraqueJuan Carlos López-RodríguezJavier RojoCristobalina MayorgaMayte VillalbaEva BataneroPublished in: Molecular pharmaceutics (2020)
Olive pollen is one of the most important causes of respiratory allergy, with Ole e 1 being the most clinically relevant sensitizing allergen. Peptide-based vaccines represent promising therapeutic approaches, but the use of adjuvants is required to strengthen the weak immunogenicity of small peptides. We propose the use of dendrimeric scaffolds conjugated to the T cell immunodominant epitope of Ole e 1 (OE109-130) for the development of novel vaccines against olive pollen allergy. Four dendrimeric scaffolds containing an ester/ether with nine mannoses, an ester succinimidyl linker with nine N-acetyl-glucosamine units or nine ethylene glycol units conjugated to OE109-130 peptide were designed, and their cytotoxicity, internalization pattern, and immunomodulatory properties were analyzed in vitro. None of the dendrimers exhibited cytotoxicity in humanized rat basophil (RBL-2H3), human bronchial epithelial Calu-3, and human mast LAD2 cell lines. Confocal images indicated that mannosylated glycodendropeptides exhibited lower colocalization with a lysosomal marker. Moreover, mannosylated glycodendropeptides showed higher transport tendency through the epithelial barrier formed by Calu-3 cells cultured at the air-liquid interface. Finally, mannosylated glycodendropeptides promoted Treg and IL10+Treg proliferation and IL-10 secretion by peripheral blood mononuclear cells from allergic patients. Mannosylated dendrimers conjugated with OE109-130 peptide from Ole e 1 have been identified as suitable candidates for the development of novel vaccines of olive pollen allergy.
Keyphrases
- endothelial cells
- atopic dermatitis
- photodynamic therapy
- end stage renal disease
- induced apoptosis
- infectious diseases
- newly diagnosed
- induced pluripotent stem cells
- oxidative stress
- pluripotent stem cells
- chronic kidney disease
- deep learning
- tissue engineering
- risk assessment
- patient reported outcomes
- allergic rhinitis
- cell cycle arrest