Grass Pollen Allergoids Coupled to Mannan Are Novel Vaccines with Enhanced Capacity to be Captured By Dendritic Cells Promoting Th1 Immune Responses and High Levels of IL-10
Tuesday, March 4, 2014
Exhibit Hall B (Convention Center)
Oscar Palomares, PhD, Sofia Sirvent, PhD, Irene Soria, PhD, Barbara Cases, PhD, Carmen Díez, PhD, Pedro Reche, PhD, Juan López-Relaño, PhD, Eduardo Martínez-Naves, PhD, Enrique Fernandez-Caldas, PhD, Jose Luis Subiza, MD, PhD
Rationale: The immunogenicity and efficacy of allergen vaccines depend on the capacity of dendritic cells (DCs) to capture them and to induce proper immune responses. Herein, we compared the ability of native grass pollen extracts (N), glutaraldehyde-polymerized allergoids (P) and glutaraldehyde-polymerized allergoids coupled to mannan (PM) to be internalized by DCs and to regulate immune responses.

Methods: N, P and PM Phleum pratense pollen extracts were produced. Human monocytes from buffy coats were differentiated to DCs with IL-4/GM-CSF. Allergen uptake was assessed by flow cytometry and confocal microscopy. Co-culture experiments, real-time quantitative PCR, ELISA and ELISPOT were performed. Antibody levels in serum from BALB/c mice immunized with extracts, proliferation of splenocytes and cytokine production were determined.  

Results: PM was captured by human DCs more efficiently than N or P through mechanisms partially depending on receptor-mediated internalization. DCs stimulated with N, P and PM expressed high levels of HLA-DR, CD86 and CD83. PM-activated DCs produced higher levels of IL-6 and IL-10 than N- or P-activated DCs. Allogeneic and allergen-specific co-cultures showed that PM-activated DCs generated T cells producing higher levels of IFN-gamma and IL-10 and lower levels of IL-5 or IL-4 than N- or P-activated DCs. Splenocytes from mice immunized with PM showed a Th1 cytokine-signature and high levels of IL-10 with higher proliferation than those from mice immunized with N or P.

Conclusions: Grass pollen hypoallergenic allergoids conjugated to mannan may represent safer and more effective novel vaccines due to their enhanced immunogenicity and capacity to promote Th1 mediated T cell responses to allergens.