A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

Abstract

Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH.

Solid‐in‐oil nanodispersions for transdermal drug delivery systems

“…Since the continuous phase of the S/O nanodispersions is IPM, additional use of lipophilic adjuvants, such as, TLR4 agonists monophosphory lipid A , trehalose‐6,6'‐dibehenate , and lipophilic derivatives of muramyl dipeptide , would improve the stabilization of the S/O nanodispersions, instead of merely induction of the enhanced antibody responses. Above mentioned adjuvants are also known to induce Th1‐type immunity, which is a prerequisite for protection against tuberculosis, malaria and HIV infections.…”

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

“…A plethora of animal models for specific allergen immunotherapy tried optimizing the application mode and route of allergen, by entrapment in tolerogenic PLG particles [46 ▪▪ ], or application concomitantly with CpG [45], probiotics or Vitamin D3 (Table 1) [37–39,41,42 ▪ ,43 ▪▪ ,44,45,46 ▪▪ ,49 ▪ ,51]. In particular, epicutaneous application has achieved promising results without adjuvants [43 ▪▪ ].…”

“…In particular, epicutaneous application has achieved promising results without adjuvants [43 ▪▪ ]. On the basis of therapeutic mouse studies [49 ▪ ] and preventive approaches in horses [51], the frequency of usage of the intralymphatic route is expected to increase in the near future.…”

“…Apart from atopy (Fig. 1c, f), insect bite hypersensitivity is a common problem in horses, which could be prevented by intralymphatic injections with recombinant insect allergens, adjuvanted with monophosphoryl lipid A (MPL) or aluminium hydroxide [51]. …”

EAACIposition paper: Comparing insect hypersensitivity induced by bite, sting, inhalation or ingestion in human beings and animals

“…The availability of pure recombinant allergens should improve AIT in future. The potential of prophylactic immunization using intralymphatic immunization with recombinant allergens or with transgenic barley, expressing Culicoides allergens, is currently being explored . Using an active vaccination against IL‐5 resulted in significant improvement of symptoms in nearly 50% of the treated horses, thus being a promising treatment option …”