Peanut allergy, a potentially life-threatening condition, has emerged as a major public health concern in developed countries. Strict dietary avoidance is recommended to prevent fatal anaphylactic reactions and to date, there are no safe therapeutic options to address the underlying pathogenic allergen-specific T-helper-type 2 (Th2) biased CD4⁺ T cell responses. Herein, we describe the use of a novel, proprietary Sementis Copenhagen Vector (SCV)¹ -based peanut hypoallergenic vaccine (SCV-PHAV) that encodes 11 key peanut allergens to elicit peripheral T cell tolerance by modulating the cytokine responses of peanut-specific CD4⁺ T cells. Co-cultures of dendritic cells (DCs) and CD4⁺ T cells from clinically confirmed peanut-allergic individuals were set up to investigate the capacity of SCV-PHAV instructed DCs to facilitate a tolerant Th1-biased peanut-specific CD4⁺ T cell response. An increase in peanut-specific interferon-γ producing CD4⁺T cells with a concomitant significant increase in Th1/ Th2 ratio was detected in SCV-PHAV vaccinated cultures compared to peanut-pulsed cultures. A consistent increase was observed in separate ex vivo DC: CD4 T cultures set up 6-months apart from the same patient, confirming both assay reproducibility and vaccine efficacy. In addition, we were able to demonstrate that the antigen-specific Th1 bias could be maintained long-term following culture in the presence of peanut antigens. Importantly, in vivo prophylactic vaccination studies in mice confirmed induction of peanut-specific IgG2a antibody responses in SCV-PHAV vaccinated mice upon allergen sensitization. Collectively, our data demonstrates that the SCV-PHAV vaccine can shift the peanut-reactive CD4⁺ T cell population from a pathogenic, pro-allergic Th2-biased to a tolerant, Th1-biased profile with potential to alleviate allergic symptoms.

¹ Eldi, P. et al. Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology. Mol Ther (2017)