Allergen immunotherapies are often successful at desensitizing allergic patients but can require life-long dosing and suffer from frequent adverse events including instances of systemic anaphylaxis leading to poor patient compliance and high cost. Allergen vaccines in turn can generate more durable immunological allergen desensitization with far fewer doses. However like immunotherapies allergen vaccines are often highly reactogenic in allergic patients hampering their use in therapeutic settings. In this work we utilize a peptide-based self-assembling nanofiber platform to design allergen vaccines against allergen B-cell epitopes that do not elicit systemic anaphylaxis when administered subcutaneously to allergic mice. We show that in contrast to protein vaccines nanofiber vaccines prevent leakage of allergen material into the vascular compartment a feature that likely underpins their reduced systemic reactogenicity. Further we show that our allergen vaccine platform elicits therapeutic IgG antibody responses capable of desensitizing allergic mice to allergen-induced Type I hypersensitivity reactions. Finally we have demonstrated a proof-of-concept for the therapeutic potential of nanofiber-based peanut allergen vaccines directed against peanut allergen-derived epitopes.