In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality ...of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination.
ImmunoCAP assays: Pros and cons in allergology van Hage, Marianne, MD, PhD; Hamsten, Carl, PhD; Valenta, Rudolf, MD
Journal of allergy and clinical immunology,
10/2017, Letnik:
140, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Allergen-specific IgE measurements and the clinical history are the cornerstones of allergy diagnosis. During the past decades, both characterization and standardization of allergen extracts and ...assay technology have improved. Here we discuss the uses, advantages, misinterpretations, and limitations of ImmunoCAP IgE assays (Thermo Fisher Scientific/Phadia, Uppsala, Sweden) in the field of allergology. They can be performed as singleplex (ImmunoCAP) and, for the last decade, as multiplex (Immuno Solid-phase Allergen Chip ISAC). The major benefit of ImmunoCAP is the obtained quantified allergen-specific IgE antibody level and the lack of interference from allergen-specific IgG antibodies. However, ImmunoCAP allergen extracts are limited to the composition of the extract. The introduction of allergen molecules has had a major effect on analytic specificity and allergy diagnosis. They are used in both singleplex ImmunoCAP and multiplex ImmunoCAP ISAC assays. The major advantage of ISAC is the comprehensive IgE pattern obtained with a minute amount of serum. The shortcomings are its semiquantitative measurements, lower linear range, and cost per assay. With respect to assay performance, ImmunoCAP allergen extracts are good screening tools, but allergen molecules dissect the IgE response on a molecular level and put allergy research on the map of precision medicine.
More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused the unforeseen COVID-19 pandemic with millions of deaths. In the meantime, SARS-CoV-2 has become ...endemic and is now part of the repertoire of viruses causing seasonal severe respiratory infections. Due to several factors, among them the development of SARS-CoV-2 immunity through natural infection, vaccination and the current dominance of seemingly less pathogenic strains belonging to the omicron lineage, the COVID-19 situation has stabilized. However, several challenges remain and the possible new occurrence of highly pathogenic variants remains a threat. Here we review the development, features and importance of assays measuring SARS-CoV-2 neutralizing antibodies (NAbs). In particular we focus on in vitro infection assays and molecular interaction assays studying the binding of the receptor binding domain (RBD) with its cognate cellular receptor ACE2. These assays, but not the measurement of SARS-CoV-2-specific antibodies per se, can inform us of whether antibodies produced by convalescent or vaccinated subjects may protect against the infection and thus have the potential to predict the risk of becoming newly infected. This information is extremely important given the fact that a considerable number of subjects, in particular vulnerable persons, respond poorly to the vaccination with the production of neutralizing antibodies. Furthermore, these assays allow to determine and evaluate the virus-neutralizing capacity of antibodies induced by vaccines and administration of plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 variants or synthetic compounds to be used for therapy of COVID-19 and assist in the preclinical evaluation of vaccines. Both types of assays can be relatively quickly adapted to newly emerging virus variants to inform us about the magnitude of cross-neutralization, which may even allow us to estimate the risk of becoming infected by newly appearing virus variants. Given the paramount importance of the infection and interaction assays we discuss their specific features, possible advantages and disadvantages, technical aspects and not yet fully resolved issues, such as cut-off levels predicting the degree of in vivo protection.
Background House dust mites (HDMs) represent one of the most important inducers of respiratory allergies worldwide. Objective We sought to investigate the IgE and IgG reactivity profiles to a ...comprehensive panel of HDM allergens in children with allergic asthma and to compare them with those of nonasthmatic atopic children. Methods Sera from clinically well-characterized asthmatic children with HDM allergy (n = 105), nonasthmatic children (n = 53), and nonatopic nonasthmatic children (n = 53) were analyzed for IgE and IgG reactivity to a panel of 7 HDM allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 21, and rDer p 23) by means of allergen microarray technology. Results Asthmatic children with HDM allergy more frequently showed an IgE response to each of the HDM allergens and recognized more allergens than nonasthmatic children with HDM allergy. Furthermore, IgE levels to certain HDM allergens (nDer p 1, P = .002; rDer p 2, P = .007; rDer p 5, P = .031; and rDer p 23, P < .001) were significantly higher in asthmatic children than in children without asthma. By contrast, fewer asthmatic children showed IgG reactivity to HDM allergens than nonasthmatic children, but allergen-specific IgG levels were comparable. Conclusion The IgE and IgG reactivity profiles to HDM allergens, as well as IgE levels to certain allergen components, differed considerably between children with and without asthmatic symptoms caused by HDM allergy. In fact, asthmatic children were characterized by an expanded IgE repertoire regarding the numbers of recognized allergen components and by increased specific IgE levels.
More than 25% of the population in industrialized countries suffers from immunoglobulin-E-mediated allergies. The antigen-specific immunotherapy that is in use at present involves the administration ...of allergen extracts to patients with the aim to cure allergic symptoms. However, the risk of therapy-induced side effects limits its broad application. Recent work indicates that the epitope complexity of natural allergen extracts can be recreated using recombinant allergens, and hypoallergenic derivatives of these can be engineered to increase treatment safety. It is proposed that these modified molecules will improve the current practice of specific immunotherapy and form a basis for prophylactic vaccination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. Objectives We sought to characterize the evolutionary patterns of ...the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. Methods We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. Results One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Conclusions Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
Background Sensitization to individual cat and dog allergen molecules can contribute differently to development of allergy to these animals. Objective We sought to investigate the association between ...sensitization patterns to cat and dog allergen molecules during childhood and symptoms to these furry animals up to age 16 years. Methods Data from 779 randomly collected children from the Barn/Children Allergy/Asthma Milieu Stockholm Epidemiologic birth cohort at 4, 8, and 16 years were used. IgE levels to cat and dog were determined by using ImmunoCAP, and levels to allergen molecules were determined by using an allergen chip based on ISAC technology (Mechanisms for the Development of Allergy chip). Allergy was defined as reported rhinitis, conjunctivitis, or asthma at exposure to cat or dog. Results Cross-sectionally, IgE to Fel d 1 and cat extract had similar positive predictive values for cat allergy. IgE to Can f 1 showed a higher positive predictive value for dog allergy than dog extract IgE. Sensitizations to Fel d 1 and Can f 1 in childhood were significantly associated with symptoms to cat or dog at age 16 years. Polysensitization to 3 or more allergen molecules from cat or dog was a better longitudinal predictor of cat or dog symptoms than results of IgE tests with cat or dog allergen extract, respectively. Cross-sectionally, cat/dog-polysensitized children had higher IgE levels and more frequent symptoms to cat and dog than monosensitized children. Conclusions Sensitization to Fel d 1 and Can f 1 in childhood and polysensitization to either cat or dog allergen molecules predict cat and dog allergy cross-sectionally and longitudinally significantly better than IgE to cat or dog extract.
Immunoglobulin E (IgE)‐mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the ...production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen‐specific IgE then binds to the high (FcεRI) and low‐affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen‐presenting cells. 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 with 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 mast cells 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.
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