Self-Assembling Allergen Vaccine Platform Raises Therapeutic Allergen-Specific IgG Responses without Induction of Systemic Allergic Responses.

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.

A sublingual nanofiber vaccine to prevent urinary tract infections.

Urinary tract infections (UTIs) are a major public health problem affecting millions of individuals each year. Recurrent UTIs are managed by long-term antibiotic use, making the alarming rise of antibiotic resistance a substantial threat to future UTI treatment. Extended antibiotic regimens may also have adverse effects on the microbiome. Here, we report the use of a supramolecular vaccine to provide long-term protection against uropathogenic Escherichia coli, which cause 80% of uncomplicated UTIs. We designed mucus-penetrating peptide-polymer nanofibers to enable sublingual (under the tongue) vaccine delivery and elicit antibody responses systemically and in the urogenital tract. In a mouse model of UTI, we demonstrate equivalent efficacy to high-dose oral antibiotics but with significantly less perturbation of the gut microbiome. We also formulate our vaccine as a rapid-dissolving sublingual tablet that raises response in mice and rabbits. Our approach represents a promising alternative to antibiotics for the treatment and prevention of UTIs.