Intranasal, Liposome-Adjuvanted Cockroach Allergy Vaccines Made of Refined Major Allergen and Whole-Body Extract of <b><i>Periplaneta americana</i></b>

Abstract

Background: Cockroach (CR) allergens frequently cause severe asthma in CR-sensitized subjects. Allergen-specific immunotherapy causes a shift of allergic Th2 responses towards Th1 and/or regulatory T cell (Treg) responses which reduce airway inflammation and prevent disease progression. Data are relatively limited on immunotherapy via CR allergy vaccine. Methods: The therapeutic efficacy of an intranasal liposome-adjuvant vaccine made of a refined Periplaneta americana arginine kinase (AK) was compared to the liposome-entrapped P. americana crude extract (CRE) vaccine. Adult BALB/c mice were rendered allergic to CRE. Three allergic mouse groups were immunized intranasally on alternate days with 8 doses of liposome-entrapped CRE (L-CRE), liposome-entrapped AK and placebo, respectively. One week later, all mice received a nebulized CRE provocation. Evaluation of vaccine efficacy was performed 1 day after provocation. Results: Liposome-entrapped native AK attenuated airway inflammation after the CRE provocation and caused a shift of allergic Th2 to Th1 and Treg responses. The L-CRE also induced a shift from the Th2 to the Th1 response but did not induce a Treg response and could not attenuate the airway inflammation upon allergen reexposure. Conclusions: Intranasal liposome-adjuvant CR allergy vaccine containing native AK (Per a 9) is better than L-CRE in attenuating allergic airway inflammation. The findings of this study not only document a more comprehensive and beneficial immune response induced by the refined allergen vaccine but also raise the point that the shift from the Th2 to the Th1 response alone might not correlate with improved airway histopathology, clinical outcome and quality of life.

New Insights into Cockroach Allergens

“…Per a 9, despite its low stability, is one of the most abundant cockroach allergens in Taiwanese patient’s homes, indicating current status of cockroach control [56]. Intranasal, liposome-adjuvanted allergy vaccines made of Per a 9 resulted in better attenuation of allergic airway inflammation in a mouse model than the equivalent vaccine made with whole-body extract from P. americana [105]. Recently, Bla g 9 has been found to be an immunodominant allergen regarding T cell responses in asthmatic subjects ●[106].…”

Nanoparticle&ndash;allergen complexes for allergen immunotherapy

“…Furthermore, this study demonstrated that IN liposome adjuvanted cockroach allergens containing native Per a 9 are more effective than complexes with liposome and crude extracts at attenuating allergy airway inflammation and allowing a more precise standardization of the product. 80 Refer to Table 2 for a summary of this section. Another relevant feature of these types of complexes was introduced by Weinberger et al who showed that the coupling of a carbohydrate to a protein can mask B-cell epitopes, making the protein "hypoallergenic".…”

Cockroach Allergy and Its Immunotherapy

“…Amerikan hamamböceğine yönelik immünoterapi uygulamalarına, major allerjen ve tüm vücut ekstraktını içeren lipozom-adjuvanlı intranazal kullanılan aşılar eklenmiştir (49). Yine tüm bu zorluklardan dolayı, teşhis ve tedavide kullanılacak rekombinan allerjenler geliştirilmeye çalışılmaktadır (50 Hamamböceğine duyarlı ve evlerinde maruz kalmaya (Bla g 1 düzeyi: ≥2 U/g) devam eden bir grup hastanın Omalizumab'tan çok faydalandığı görülmüştür.…”