2020 EJRNL PP Sara Benede? -1.pdf
Terbatas Irwan Sofiyan
» ITB
Terbatas Irwan Sofiyan
» ITB
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-acetylglucosamine
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.