These vaccines are simple approaches but remarkable innovations originate from two most successful immunological treatments in the history of allergic disease, histamine-immunoglobulin complex treatment (50 years) and allergen-specific immunotherapy (100 years). With the technology platform, two types of immunoglobulin-based allergy vaccines were developed: (a) type I vaccines comprising histamine and allergen-specific antibody; and (b) type II vaccines comprising histamine, immunoglobulin and allergen.
(1) Vaccine Comprising Histamine and Allergen-Specific Antibody (Type I Vaccine)
Background and unmet needs: Although a current form of a polyclonal human immunoglobulin-based non-specific immunotherapy using histamine-immunoglobulin complex has been successfully used for about 50 years in Europe, Japan, America, and Russia, this treatment is not currently regarded as a standard treatment option in the international guidelines for allergic diseases.
Generally, physicians believes a clinical efficacy of the conventional histamine-immunoglobulin complex but judge that its clinical efficacy is not significantly better than other current standard pharmacological treatments. Moreover, the anti-allergic action mechanism of currently used histamine-immunoglobulin complex has not been completely understood.
Discovery and achievements: In considering shortcomings of current allergy therapeutics, the ‘Type I Vaccine’ takes a giant step to control allergic responses to causative allergens as an inovation from the pre-existing histamine-immunoglobulin complex. The Type I Vaccine comprises hisamine and allergen-specific antibody.
A synergistically enhanced anti-allergic efficacy between histamine and allergen-specific antibody was discovered. Based on the findings and results of further experiments, we finally formulated vaccines comprising hisamine and allergen-specific antibody having anti-allergic efficacy of both histamine-nonspecific immunoglobulin complex and passive immunotherapy with allergen-specific immune globulin that has been clinically proven for a long time.
(2) Vaccine Comprising Histamine, Immunoglobulin and Allergen (Type II Vaccine)
Background and unmet needs: Atopic dermatitis is affecting major portions of population (up to 30% prevalence in Northern Europe) and there is no clearly effective and safe treatment for patients with severe atopic dermatitis. Recently developed topical calcineurin inhibitors (pimecrolimus from Novartis or tacrolimus from Astellas) have been claimed for possible risk of skin cancer by FDA. Treatment with anti-IgE monoclonal antibody (omalizumab) also showed equivocal clinical effects for atopic dermatitis.
Discovery and achievements: A main idea for the invention was a combination of two traditional immunotherapy methods which has already been used for the treatments of allergic diseases for a long time. One is an allergen-immunotherapy with history of about 100 years but this treatment has not been regarded effective for the treatment of atopic dermatitis. Another one is a non-specific immunotherapy using histamine-immunoglobulin complex which has been successfully used world-widely for about 50 years.
The Type II vaccine composition comprises histamine, immunoglobulin and allergen. We have successfully treated about 100 patients with severe recalcitrant atopic dermatitis with the Type II vaccine.
Surprisingly, human clinical trial demonstrated a significant clinical improvements of atopic dermatitis (same or greater than 50% from baseline severity) was observed in 90% of treated patients with atopic dermatitis after 12 months of the treatment without any side effects. And a synergistic interaction among three components of our Type II vaccine was demonstrated as follows: The clinical efficacy of a composition comprising histamine, immunoglobulin, and allergen was not reproduced by immunoglobulin and allergen in same doses without histamine. And a separate injection of histamine-immunoglobulin complex and allergen in each arms resulted in marked decrease of clinical efficacy. The composition comprising histamine, immunoglobulin, and allergen is a safe and effective biological therapeutics for allergic diseases.
(3) Exclusiveness and Expandability of the Type I and Type II Vaccines
The use of different allergen-specific antibody instead of normal polyclonal human immunoglobulin according to hypersensitivity to various kinds of allergens in each patient with allergic diseases provides a unique exclusiveness of the two types of vaccines. And those can be further developed as a more powerful and exclusive composition if a current recombinant human antibody technique is applied.