Allergenics are biologic preparations used for the diagnosis and treatment of allergic diseases.
They contain allergens or allergen extracts derived from natural sources such as pollens, dust mites, molds, animal danders, insect venoms, or foods.
Allergenics are primarily used in:
- Allergy testing (skin prick, intradermal, patch testing)
- Allergen immunotherapy (AIT) — a therapeutic approach designed to modify immune response and induce long-term tolerance to specific allergens
The use of allergenics represents a disease-modifying approach, unlike antihistamines or corticosteroids that only control symptoms.
2. Immunologic Background
Allergic diseases (e.g., allergic rhinitis, asthma, atopic dermatitis) are IgE-mediated hypersensitivity reactions.
- Sensitization Phase:
- Exposure to an allergen → activation of Th2 lymphocytes → production of IgE antibodies
- IgE binds to FcεRI receptors on mast cells and basophils
- Re-exposure Phase:
- Allergen cross-links IgE on mast cells → degranulation → release of histamine, leukotrienes, cytokines
- Leads to clinical symptoms (sneezing, itching, wheezing)
- Therapeutic Strategy:
- Allergenics (immunotherapy) aim to induce tolerance by shifting immune response from Th2 to Th1 and increasing regulatory T cells (Tregs) and IgG4 blocking antibodies.
3. Classification of Allergenic Products
| Type | Examples | Purpose |
|---|---|---|
| Diagnostic allergen extracts | Pollens (ragweed, grass, tree), dust mites, animal dander | Used for skin testing to identify specific sensitivities |
| Therapeutic allergen extracts (immunotherapy) | Standardized allergen extracts | Used for subcutaneous (SCIT) or sublingual (SLIT) immunotherapy |
| Venom immunotherapy | Bee, wasp, hornet venom extracts | Used for anaphylaxis prevention in insect-sting allergies |
| Food allergen extracts | Peanut, milk, egg (under clinical evaluation) | Used experimentally for oral desensitization |
4. Mechanism of Action (in Immunotherapy)
Allergen immunotherapy works through immune modulation:
- ↓ Allergen-specific IgE production
- ↑ Allergen-specific IgG4 (“blocking antibody”) that competes with IgE for antigen binding
- ↓ Mast cell and basophil reactivity
- ↑ Regulatory T-cell activity → production of IL-10 and TGF-β
- Shift from Th2 (allergic) to Th1 (non-allergic) response
This leads to reduced allergic inflammation and long-term clinical tolerance, even after discontinuing therapy.
5. Pharmacologic Forms
| Formulation | Route of Administration | Notes |
|---|---|---|
| Aqueous extracts | Subcutaneous (SCIT) | Require medical supervision; risk of systemic reaction |
| Alum-precipitated extracts | Subcutaneous | Slower absorption, fewer reactions |
| Sublingual tablets/drops (SLIT) | Oral/sublingual | Self-administered; safer but slightly less potent |
| Modified allergens (allergoids) | Subcutaneous or sublingual | Chemically modified to reduce allergenicity but preserve immunogenicity |
6. Clinical Uses
- Allergic Rhinitis and Conjunctivitis
- Grass pollen, ragweed, dust mite, cat, or tree pollen extracts
- Allergic Asthma
- In patients with mild to moderate disease and confirmed IgE-mediated sensitization
- Insect Venom Allergy
- Venom immunotherapy reduces risk of anaphylaxis by up to 95%
- Atopic Dermatitis (select cases)
- For patients with proven aeroallergen triggers
- Experimental Use in Food Allergies
- Peanut or milk desensitization under strict medical supervision
7. Dosing and Administration
- Initiation Phase: Gradual dose escalation (weekly or biweekly) until maintenance dose achieved.
- Maintenance Phase: Fixed dose every 2–4 weeks for 3–5 years (SCIT) or daily (SLIT).
- Supervision: Initial doses administered under medical observation (due to anaphylaxis risk).
8. Adverse Reactions
| Type | Manifestations | Management |
|---|---|---|
| Local | Erythema, pruritus, swelling at injection site | Ice packs, antihistamines |
| Systemic (mild) | Sneezing, urticaria, wheezing | Oral antihistamines |
| Systemic (severe) | Anaphylaxis (rare) | Epinephrine, airway management, IV fluids |
| SLIT reactions | Oral itching, throat irritation | Usually self-limited |
Note: Patients receiving subcutaneous immunotherapy must remain under observation for at least 30 minutes after injection.
9. Contraindications
- Uncontrolled asthma
- Active autoimmune disease
- Malignancy
- Beta-blocker therapy (interferes with epinephrine efficacy)
- Pregnancy (initiation contraindicated; maintenance may continue with caution)
10. Monitoring and Follow-Up
- Skin prick or serum IgE testing before initiation
- Peak flow or spirometry in asthmatic patients
- Regular follow-up every 3–6 months to assess response
- Observation after each dose for systemic reactions
- Periodic re-evaluation of allergen exposure and necessity of continuation
11. Clinical Efficacy
Multiple meta-analyses and long-term studies have shown that allergen immunotherapy:
- Reduces symptom severity and medication use
- Improves quality of life
- Provides long-term tolerance (up to 10 years post-therapy)
- Reduces risk of developing new allergies or asthma onset
12. Emerging Therapies
- Recombinant allergens: Molecularly defined allergens with reduced variability
- Peptide-based vaccines: Target T-cell epitopes only; minimize IgE binding
- DNA and mRNA allergen vaccines: Under preclinical and clinical evaluation
- Epicutaneous immunotherapy: Allergen patches (especially for peanut allergy)
13. Summary Table
| Aspect | Details |
|---|---|
| Mechanism | Induction of immune tolerance via T-cell and antibody modulation |
| Main Uses | Allergic rhinitis, asthma, venom allergy |
| Administration | Subcutaneous (SCIT), Sublingual (SLIT) |
| Adverse Effects | Local reactions, anaphylaxis (rare) |
| Duration | Typically 3–5 years |
| Outcome | Long-term reduction in symptoms and medication need |
14. Summary
Allergenics represent the only disease-modifying therapy for IgE-mediated allergic disorders.
Through controlled exposure to allergens, these agents reprogram immune tolerance, offering sustained benefits beyond symptom relief.
While safety concerns (notably anaphylaxis) necessitate medical supervision, modern formulations like SLIT and allergoids have significantly improved safety and patient adherence.
Continued research into recombinant allergens and peptide vaccines promises even safer and more precise allergy management in the future.
15. References
- Canonica GW, et al. Allergen immunotherapy: the state of the art according to World Allergy Organization. World Allergy Organ J. 2019;12(3):100076.
- Cox L, et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–S55.
- Durham SR, et al. Sublingual immunotherapy for allergic rhinitis. N Engl J Med. 2006;354:2256–2265.
- Nelson HS. Advances in allergen immunotherapy. J Allergy Clin Immunol. 2020;145(2):445–454.
- Global Initiative for Asthma (GINA) Guidelines, 2024.
- FDA Center for Biologics Evaluation and Research (CBER): Allergenics Overview.
