Modulation of T and B cell Responses by Virus-like particle (VLP) Expressing Peanut Allergen Ara h 2: A Novel Vaccine Candidate for Peanut Allergy

A cucumber mosaic virus-like particle (VLP) expressing the major peanut allergen Ara h 2 on its surface has been developed as a therapeutic approach for peanut allergy. Peripheral blood mononuclear cells (PBMCs) were enriched from six peanut-allergic subjects (aged 6-18). Effect of whole peanut extract (WPE), recombinant Ara h 2 (Ara h 2) or VLP Peanut with/without microcrystalline tyrosine [MCT] on T cells, B regulatory (Bregs) and dendritic cells (DCs), were quantified using flow cytometry and qRT-PCR. VLP Peanut had reduced capacity to elicit proliferation of ICOS+ TFH when compared to WPE (P<0.05). Lower proliferation of Th2, Th2A, IL-4+- and IL-21+-TFH cells was observed in response to VLP Peanut, though an induction IL-10+ TFH cells was observed in response to VLP Peanut compared to Ara h 2 and WPE. VLP Peanut, with/without MCT, elicited reduced allergen-IgE complexes binding to CD23 on the surface of B cells when compared to Ara h 2 or WPE (all, P<0.01). VLP Peanut, irrespective of MCT, significantly induced IFN-g+ Th1 cells and was most prominent at generating IL-10-producing CD19+CD5hi and CD19+CD27+ Bregs compared Ara h 2 and WPE (all, P<0.05). CD141 and GATA3, markers of pro-allergic DCs, were downregulated whilst MX1 and FSCN1, markers of DC1 were upregulated following stimulation with VLP Peanut compared to Ara h 2 or WPE. We demonstrate that VLP Peanut has the potential to modulate T, B and dendritic cell responses, promoting the protective tolerogenic pathway. These results highlight the potential therapeutic use of VLP Peanut for peanut allergy.