Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.
Advances in molecular biology alongside the accelerated development of gene and cell engineering have contributed to the development of several endotype-targeted biological therapies against chronic immune-mediated allergic diseases. Conventional therapies for asthma, chronic rhinosinusitis with polyposis (CRSwNP), chronic spontaneous urticaria and atopic dermatitis (AD) are not without limitations, and as such the advent of biological therapies have provided a promising alternative treatment option. Biologicals have proven efficacious in the treatment of refractory chronic spontaneous urticaria, asthma, AD, CRSwNP and there is increasing evidence for their utility in treating food allergy. Biologicals are applied and investigated for the most urgent need: acute treatment, symptom control and reduction of steroid usage. Currently there are five approved biologicals for allergic disease management, targeted against IgE (omalizumab), type 2 (T2) cytokines and cytokine receptors (IL-4Ra; dupilumab, IL-5; mepolizumab/reslizumab, IL-5Ra; benralizumab).
Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.
Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
Food allergy is an increasingly common disease worldwide, and is thought to be driven by an uncontrolled type 2 immune response. Current knowledge about the underlying mechanisms that initiate and promote an inappropriate immune response to dietary allergens is limited. Sensitization through the skin in early life is considered to be a key event. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils during acute reactions. Recent data implies a possible role of innate lymphoid cells (ILCs) in driving food allergy. ILCs represent a group of lymphocytes that lack specific, recombined antigen receptors. They contribute to immune responses not only through the release of cytokines and other mediators, but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidences on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.
Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current guidelines, which exclude patients with severe allergies from vaccination with BNT162b2, should be re-evaluated after more information and experience with the new vaccine develops.