BackgroundHouse dust mite (HDM) extract based allergen immunotherapy (AIT) to treat HDM allergy is substantially effective but still presents some safety and efficacy concerns that warrant improvement. Several major allergen-based approaches to increase safety and efficacy of AIT have been proposed. One of them is the use of the group 2 allergen, Der p 2. ObjectiveIn this study, we investigated the immunomodulatory effects of sialic acid-modified major allergen recombinant Der p 2 (sia-rDer p 2) on PBMCs from healthy volunteers. MethodsWe activated PBMCs with anti-CD3/CD28 antibodies and incubated them at 37°C for 6 days in the presence or absence of either native rDer p 2 or α2-3 sialic acid-modified rDer p 2 (sia-rDer p 2). We assessed the changes in CD4+T cell activation and proliferation by flow cytometry and changes in T lymphocyte cytokine production in cell culture supernatant by ELISA. ResultsWe observed that, PBMCs treated with sia-rDer p 2 presented with a markedly decreased expression of CD69 and an increased abundance of LAG-3+ lymphocytes compared to cells treated with rDer p 2. Moreover, PBMCs treated with sia-rDer p 2 showed a reduced production of IL-4, IL-13 and IL-5 and displayed a higher IL-10/IL-5 ratio compared to rDer p 2-treated PBMCs. ConclusionWe demonstrate that α2-3 sialic acids-modified rDer p 2 might be a safer option than native rDerp2 for Der p 2-specific AIT. This is most relevant in the early phase of AIT that is often characterized by heightened Th2 responses, as sia-rDer p 2 does not enhance the production of Th2 cytokines.