Rationally Designed Allergy Vaccines

Designing synthetic antigens that reprogram allergic immune memory toward durable, healthy responses — moving precision allergy vaccines toward the clinic.
Ongoing Allergic & Atopic Diseases Adaptive Immunity Animal Models B Cell Biology Biological & Mechanistic Experimental Platforms & Models Immune Tolerance Therapeutic Development Translational & Clinical

Funding Year: 2024

Project Overview

Allergic and non-allergic individuals share immune memory of allergens, but in allergic individuals that memory is improperly tuned — driving overreactive, potentially fatal responses upon allergen exposure. Because healthy and allergic immune memories are self-sustaining and antagonistic, permanently altering the allergic state has proven difficult. This project develops a precision approach: using epitope screening to identify key antibody reactivities in the allergic state, then designing synthetic antigens that evade allergic memory while inducing healthy responses. Experimental evidence shows the allergic state can be durably reduced in mice using this vaccine strategy. The team is now refining the molecular approach to translate these findings into effective, long-lasting allergy vaccines for human use.

Impact & Innovation

Reprogramming allergic memory at the molecular level.

 

By mapping the antibody reactivities that define the allergic state and designing synthetic antigens to redirect them, this project offers a rationally designed path to durable allergy resolution — not just symptom management.

  • Demonstrates that allergic immune memory can be durably reduced using synthetic antigens that evade allergic responses while inducing protective ones — a fundamental mechanistic advance
  • Generates IP potential through precision epitope screening tools and synthetic antigen designs tailored to drive durable, protective immune responses against food allergens
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar by illuminating how immune memory dysregulation drives allergic disease, with implications for tolerance restoration across autoimmune and allergic conditions
Research Approach

A framework designed for discovery

This project combines precision epitope screening, synthetic antigen design, and in vivo immune memory modeling to develop rationally designed allergy vaccines capable of durably reprogramming the allergic state. The work moves from molecular characterization of allergic antibody reactivities through vaccine design and preclinical validation.

Precision epitope screening to identify key antibody reactivities present in the allergic state, using peanut epitopes as a clinically relevant allergen model; design and synthesis of antigens that evade allergic memory while inducing healthy immune responses; and in vivo testing in allergic mouse models to assess durable reduction of the allergic state.

Peanut allergen epitope screening datasets identifying stereotypic and predictable antibody responses, allergic and non-allergic immune memory profiling data, experimental vaccine response datasets from allergic mouse models, and immune response data following exposure to exogenous proteins similar to but not identical with peanut proteins.

Development and validation of synthetic antigens capable of shifting immune responses away from the allergic state, with the translational goal of producing effective, long-lasting allergy vaccines for human use. Findings will guide refinement of the molecular approach needed to advance precision allergy vaccines from preclinical models to clinical application.

Investigators & Institutions

Powering the science

Principal Investigator

Ruslan Medzhitov, PhD, Colton Consortium Member

Sterling Professor of Immunobiology, Department of Immunobiology, Yale School of Medicine, Yale University

Colton Centers & Institutions

Colton Center for Autoimmunity at Yale University

Research Outputs

From insight to impact