Peptide Glycodendrimers as Potential Vaccines for Olive Pollen Allergy

Abstract

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 (OE 109−130 ) 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 OE 109−130 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 OE 109−130 peptide from Ole e 1 have been identified as suitable candidates for the development of novel vaccines of olive pollen allergy.

Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers

“…Toward achieving these vaccine candidates, the "onion peel" type [26][27][28][29] the 22 amino acids peptide sequence 109−130 from the most prevalent all pollen (Olea europaea) (Ole e 1) (OE109-130) have been shown to represen tool in the design of novel vaccines against olive pollen allergy due to thei promoters of the T lymphocyte regulatory cells (Treg) but not as activators o efficient transport across the epithelial barrier, and no cytotoxicity (Scheme Scheme 6. Synthetic sequence leading to an "onion peel" mannosylated glycodend able as vaccine candidate against allergies caused by olive pollen [32]. Scheme 6.…”

“…These adjuvants modulate adaptive immune responses by cellular activation which have been progressively proposed for use in vaccine design. Heterobifunctional mannosylated glycodendropeptides ( 66 ) containing the 22 amino acids peptide sequence 109−130 from the most prevalent allergen of olive pollen ( Olea europaea ) (Ole e 1) (OE109–130) have been shown to represent a promising tool in the design of novel vaccines against olive pollen allergy due to their properties as promoters of the T lymphocyte regulatory cells (Treg) but not as activators of effector cells, efficient transport across the epithelial barrier, and no cytotoxicity ( Scheme 6 ) [ 32 ].…”

“… Synthetic sequence leading to an “onion peel” mannosylated glycodendropeptides suitable as vaccine candidate against allergies caused by olive pollen [ 32 ]. …”

“…Janus glycodendrimers possessing other aromatic scaffolds (5) have also been described [30]. Structure 6 with either probes or immunogenic peptides are useful as MRI contrast agents [31] or as vaccine candidates [32,33], respectively. Finally, cyclic peptides as scaffolds are interesting vaccine candidates (7) [34].…”

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

“…On the other hand, dendrimers can act as immunomodulators, by either reducing or enhancing the immune response [ 42 ]. The first approach can be very useful towards autoimmune diseases and allergies [ 43 ], while the second has been employed, for example, in cancer immunotherapy [ 44 ]. The attachment of multiple antigen copies to the dendritic scaffold produces an increase in the immune response related to the multivalency and the decrease in the conformational freedom of the antigen.…”