Abstract
Vaccines for infectious diseases have improved the life of the human species in a tremendous manner. The principle of vaccination is to establish de novo adaptive immune response consisting of antibody and T cell responses against pathogens which should defend the vaccinated person against future challenge with the culprit pathogen. The situation is completely different for immunoglobulin E (IgE)-associated allergy, an immunologically-mediated hypersensitivity which is already characterized by increased IgE antibody levels and T cell responses against per se innocuous antigens (i.e., allergens). Thus, allergic patients suffer from a deviated hyper-immunity against allergens leading to inflammation upon allergen contact. Paradoxically, vaccination with allergens, termed allergen-specific immunotherapy (AIT), induces a counter immune response based on the production of high levels of allergen-specific IgG antibodies and alterations of the adaptive cellular response, which reduce allergen-induced symptoms of allergic inflammation. AIT was even shown to prevent the progression of mild to severe forms of allergy. Consequently, AIT can be considered as a form of therapeutic vaccination. In this article we describe a strategy and possible road map for the use of an AIT approach for prophylactic vaccination against allergy which is based on new molecular allergy vaccines. This road map includes the use of AIT for secondary preventive vaccination to stop the progression of clinically silent allergic sensitization toward symptomatic allergy and ultimately the prevention of allergic sensitization by maternal vaccination and/or early primary preventive vaccination of children. Prophylactic allergy vaccination with molecular allergy vaccines may allow halting the allergy epidemics affecting almost 30% of the population as it has been achieved for vaccination against infectious diseases.
Highlights
Since the classical experiment in which Edward Jenner vaccinated for the first time with cowpox to protect against smallpox infections in 1796 much has been achieved in the field of vaccination against infectious diseases [1,2,3] and against cancer [4]
Prophylactic vaccines are available for infectious diseases but not yet for immunoglobulin E (IgE)-associated allergy, the most common immune mediated hypersensitivity disease
With the molecular characterization of the disease-causing allergens, new forms of molecular Allergen-specific immunotherapy (AIT) have been developed of which B cell epitope-based peptide carrier vaccines have been evaluated in several clinical trials and were found to exhibit several characteristics which make them possible candidates for prophylactic allergy vaccination
Summary
Since the classical experiment in which Edward Jenner vaccinated for the first time with cowpox to protect against smallpox infections in 1796 much has been achieved in the field of vaccination against infectious diseases [1,2,3] and against cancer [4]. The wildtype-like recombinant allergens contain the IgE and T cell epitopes of the corresponding natural allergens It is known from subcutaneous injection AIT (SCIT) trials performed with a mixture of recombinant grass pollen allergens and with recombinant major birch pollen allergen Bet v 1 that vaccination induces allergen-specific IgG antibodies which inhibit IgE binding to the allergen [43, 44]. Carrier-bound B cell epitope-containing peptide vaccines have been developed for several important allergen sources including pollen from trees, grasses, weeds, cats, house dust mites to name a few [68] These molecules have been characterized regarding their structural and immunological features in vitro and in vivo in animal models regarding their ability to induce IgG antibody responses which can block allergic patient’s IgE binding to the natural allergens [75]. Designation in the ClinicalTrials.gov database of privately and publicly funded clinical studies conducted around the world
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