# New dietary trends and alternative proteins: the emergence of novel food allergens

Yara Awad, Hervé Bernard, Karine Adel-Patient, Stéphane Hazebrouck

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Yara Awad, Hervé Bernard, Karine Adel-Patient, Stéphane Hazebrouck. New dietary trends and alternative proteins: the emergence of novel food allergens. Current Opinion in Clinical Nutrition and Metabolic Care, 2025, 28 (1), pp.44-49. 10.1097/MCO.0000000000001081. hal-05194169

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# New dietary trends and alternative proteins: the emergence of novel food allergens

Yara Awad, Hervé Bernard, Karine Adel-Patient and Stéphane Hazebrouck

**Purpose of review**

New dietary trends driven by environmental and health considerations will undoubtedly lead to the emergence of novel food allergens. Assessment of the allergenic risk of new or modified protein-containing food sources and ingredients, as well as surveillance of emerging food allergies, is then required.

**Recent findings**

Developments of *in silico* and *in vitro* models apprehending protein capacity to cross-react with other homologous proteins and to induce a *de novo* allergic sensitization are ongoing to better integrate multiple parameters such as 3D structural information or major histocompatibility complex class II (MHC-II) presentation propensity. However, the effects of food matrices and food processing still need to be addressed in these models. Consequently, clinical and postmarket surveillance remain of critical importance to alert on emergent food allergies, which are modulated by regional dietary practices.

**Summary**

Monitoring of the emergence of food allergens requires close collaborations between allergologists, consumers, patient associations and food safety authorities. We also need to get a consensus on an acceptable level of allergenic risk that offers the possibility to develop and market innovative and sustainable food products.

**Keywords**

allergen, cross-reactivity, *de novo* sensitization, novel food, risk assessment

## INTRODUCTION

Sustainable production of dietary proteins to support the world population growth is a major challenge that requires the use of new protein-rich food sources alternative to animal products. Not only for environmental considerations toward climate change mitigation, but also for potential health benefits, the demand for innovative food products in response to new dietary trends (plant-based diets, meat-fish-egg substitutes, edible insects) is high [1]. Their development includes novel utilizations and processing of existing protein sources as well as the introduction of new protein sources that were not (or rarely) consumed by some populations [2-4]. However, along with the changes of dietary habits, the increasing level of exposure to new food ingredients inevitably paves the way for the emergence of novel food allergens. In this review, we focused on the recent developments to assess food allergenic risks, illustrated with the current evaluation of insect and legume proteins, and on the recent identification of emerging food allergens.

## FOOD ALLERGIES: IMMUNE MECHANISMS, PREVALENCE AND MAJOR ALLERGENIC FOODS

Food allergy (FA) is an adverse reaction to foods that occurs in genetically predisposed individuals who develop a sensitization towards normally innocuous proteins by producing, in most cases, specific IgE antibodies [3]. Such sensitization can be evidenced by performing allergy skin-prick tests and blood tests to measure serum levels of food- or protein-specific IgE antibodies [4]. Upon allergen ingestion, symptoms can then occur within minutes to 2 h after exposure, with anaphylaxis representing the most severe reaction. The FA prevalence varies

<footnote>Université Paris Saclay, CEA, INRAE, MTS/Laboratoire d'Immuno-Allergie Alimentaire, Gif-sur-Yvette, France</footnote>

<footnote>Correspondence to Stéphane Hazebrouck, CEA de Saclay, bât. 136, RTE DP 36, 91191 Gif-sur-Yvette cedex, France.</footnote>

<footnote>Tel: +33 1 69 08 90 41; e-mail: stephane.hazebrouck@cea.fr</footnote>

<footnote>**Curr Opin Clin Nutr Metab Care** 2025, 28:44-49</footnote>

<footnote>DOI:10.1097/MCO.0000000000001081</footnote>
## KEY POINTS

* Along with new dietary trends, we must anticipate the emergence of novel elicitors of anaphylaxis.

* Risk of immunoglobulin E cross-sensitization between new foods and known allergens is rather well assessed but provides no indication on the expected clinical potency.

* Risk assessment of de novo sensitization poses a bigger challenge and requires the development of reliable and validated in silico and in vitro predictive models.

* Clinical surveillance of food allergy emergence already reported cases of primary sensitization to increasingly consumed legumes and insects.

* Processing of food sources by different technologies offers alternatives to reduce food protein allergenicity.

greatly around the world, affecting about 8% of children and 10% of adults in developed countries [5]. Depending on the culinary culture and dietary practices, major allergenic foods also vary worldwide. Those major allergens are included in priority allergen lists, with mandatory labeling to protect allergic patients. Most of them include milk, egg, peanut, soybean, tree-nut, crustacean, fish and cereals containing gluten but, taking the EU as an example, other priority allergens can be added such as molluscs, mustard, celery, sesame or lupin [6]. Recently, a series of ad hoc joint FAO/WHO expert consultations established a watch list of allergens which may cause increasing cases of anaphylaxis because of changing/increasing use in food production. This list included different legumes (pea (protein concentrate), lentils, chickpeas), seeds (sunflower, poppy, cotton), kiwifruit and buckwheat [6]. In addition, the allergenic risk of truly novel fruits, vegetables, insects, microalgae, duckweed or fungi, whose consumption is also increasing, needs to be carefully evaluated (Table 1, [7–27]). Current guidance for allergenicity risk assessment relies on a weight-of-evidence approach and must answer two questions: is there a risk of IgE cross-reaction with already known allergens and is there a potential to induce de novo FA?

## CROSS-REACTIVITY RISK ASSESSMENT

Allergen cross-reactivity relies on the binding of at least two allergens by specific IgE antibodies, primarily raised against one of the cross-reactive allergens [28*]. The assessment of the cross-reactivity risk is quite well defined by establishing phylogenetic relationships, common structural domains

and sequence homologies, including cross-reactive IgE epitopes, between novel foods (NF) and known allergenic sources. This evaluation is then completed by studying the digestibility of food proteins and their capacity to be recognized by IgE antibodies from allergic patients [2*]. Current developments of *in silico* models include integrating MHC-II presentation propensity or 3D structural information [29*,30,31], and ranking methods of the allergenic potential associated with the clinical relevance of food allergens [32*]. This will further aid to improve NF allergen prediction and classification. It is important to note that these models are based on the primary sequence of food proteins, which is not always available for truly NFs. Current *in silico* models are particularly useful for evaluating the cross-sensitization risk of an individual protein with a yes/no answer but they provide no indication on their clinical potency [30,31]. *In silico* screening of the full genome or proteome of a NF source should also be improved as current conservative approaches to identify potential allergen cross-reactivity, such as the threshold of >35% identity over 80 amino acids, can lead to an overprediction [29*,33].

The relative concentration of allergens in the protein source, or in the processed food, is also a critical parameter that will affect the allergenic potential. Although the correlation between abundance, stability, and allergenicity is not necessarily a linear relationship [34], integration of the allergen quantification in the foodstuff would be of great value in prediction models, by excluding proteins whose concentration is below the exposure threshold of concern for allergic sensitization [35]. However, allergenicity risk assessment remains often applied on, at most, a few native proteins without taking into consideration the impact of the food matrices and the effect of the processing technologies. Different processes, such as microbial fermentation or heat, extrusion, ultrasonic and ultrahigh pressure treatments, are frequently applied on the whole source or on protein concentrates/isolates, e.g. for the production of ultra-processed meat-substitutes, and IgE-binding to the resulting processed proteins can be then significantly affected [7,19,36,37].

## DE NOVO SENSITIZATION RISK ASSESSMENT

The risk of *de novo* sensitization is much more challenging as validated strategies and methods are still missing. Some animal models have been proposed to assess the sensitization potency of food proteins [38]. A mouse model with oral sensitization
<table><caption>**Table 1.** Selected foods which pose an allergenic risk because of their increased consumption</caption><thead><tr><th>Source</th><th>Food applications<sup>a</sup></th><th>Potential cross-reactivity</th><th>Ref.</th></tr></thead><tbody><tr><td>Lentil<br>Pea<br>Chickpea</td><td>Baked goods, egg-meat substitutes, yogurt and cheese substitutes, plant-based drinks, spreads</td><td>Other legumes (mainly attributable to 7S/11S globulins)</td><td>[7–10]</td></tr><tr><td>Fenugreek</td><td>Spice, flavoring agent in baked goods</td><td></td><td></td></tr><tr><td>Poppy seeds</td><td>Baked goods, pasta, bars, yogurt drink</td><td>Tree nuts, buckwheat</td><td>[11]</td></tr><tr><td>Cotton seeds</td><td>Baked goods, dietary supplements</td><td>Peanut, tree nuts</td><td>[12]</td></tr><tr><td>Hemp seeds</td><td>Pasta, bars, plant-based drinks</td><td>Tree nuts (hazelnut), peanut, cannabis</td><td>[13]</td></tr><tr><td>Sunflower seeds</td><td>Spreads, baked goods, meat substitutes</td><td>Peanut, nuts, peach</td><td>[14,15]</td></tr><tr><td>Quinoa</td><td>Baked goods, pasta, bars, yogurt drink</td><td>Tree nuts, peanut<sup>b</sup></td><td>[16]</td></tr><tr><td>Buckwheat</td><td>Baked goods, pasta, bars, yogurt drink</td><td>Peanut, coconut, poppy, quinoa, latex</td><td>[17]</td></tr><tr><td>Kiwifruit</td><td>Smoothies, pasta and beverages</td><td>Fruit-latex: avocado, banana, birch and grass pollen, hazelnut</td><td>[18,19]</td></tr><tr><td>Pomegranate</td><td>Baked goods, dairy products</td><td>Peach, kiwifruit, tree-nuts</td><td>[20]</td></tr><tr><td>Moringa</td><td>Baked goods, pasta, meat products</td><td>Fruit-latex<sup>b</sup></td><td>[1,21,22]</td></tr><tr><td>Spirulina<br>Chlorella</td><td>Dietary supplements, beverages, pasta, bakery and dairy products</td><td>Crustaceans, fish<sup>b</sup><br>Crustaceans, fish<sup>b</sup></td><td>[23]</td></tr><tr><td>House cricket<br>Locust<br>Mealworm</td><td>Salads, soups, baked goods, pasta, snacks, beverages, meat substitutes</td><td>Crustaceans, molluscs, house dust mite</td><td>[24–27]</td></tr></tbody></table>

to sunflower seed protein was recently used to reveal the high allergenicity of the 2S-albumins Hel a 15 and Hel a 16, which were later confirmed as a potential marker of clinical severity in allergic patients [14,15]. Another recent study in Brown Norway rats suggested that quinoa poses a medium to high level of allergenicity even if case reports of quinoa allergy are rare [16]. However, the use of animal models raises ethical questions on their utility beside the investigation of immune mechanisms underlying FA development. Currently, no robust and reliable animal model has been validated in predicting the human response or in distinguishing weak from strong allergens [38]. The development of *in vitro* cell-based assays, e.g. to assess allergen transport across the intestinal barrier, epithelium activation or allergen uptake by dendritic cells and its presentation to T cells, is then urgently needed [39*]. These approaches could certainly benefit from the *in vitro* models applied to vaccine developments and protein immunogenicity prediction [40]. However, for protein allergenicity, the development of effective *in vitro* models requires a better understanding of the immune mechanisms predisposing some individuals to become allergic to foods innocuous to most people [32*].

## CROSS- AND DE NOVO SENSITIZATION TO INSECT PROTEINS

It is noteworthy that proteins capable of eliciting an allergic reaction are not necessarily the same proteins capable of inducing *de novo* sensitization [41]. A nice illustration of this discrepancy is provided by the allergenicity assessment of the yellow mealworm (YM) proteins [24–26]. By considering phylogenetic relationships between insects and crustaceans, from the same phylum Arthropoda, it was rapidly identified that the majority of shrimpfallergenic patients sensitized to crustacean panallergens, such as tropomyosin or arginine kinase, were also clinically allergic to homologous YM proteins [24]. Shrimp-allergic patients were also sensitized to a wide variety of insects, including giant mealworm, lesser mealworm, wax moth, cricket and grasshopper [26]. Scala *et al.* recently investigated the IgE sensitization to mealworm, locust (*Locusta migratoria*) and cricket (*Acheta domesticus*) proteins in individuals with various allergic conditions. Amongst the 2014 participants, 195 participants were sensitized to at least one of the extracts with 46% of them co-sensitized to the three insect extracts. However, mono-reactivity to mealworm (15%), locust (3%) and cricket (18%) was also reported [27]. Consequently, insect proteins recently added to the EU

<footnote><sup>a</sup>Beside consumption of unprocessed food.</footnote>

<footnote><sup>b</sup>Only based on *in silico* analyses and/or animal models.</footnote>
list containing all the authorized NFs should highlight the presence of these potential allergens to patients allergic to crustaceans, dust mites and molluscs, the latter one only being indicated for the presence of locust and cricket proteins [42–45].

In contrast, primary sensitization to YM proteins in individuals with no preexisting FA led to a different profile of IgE sensitization, with IgE predominantly recognizing some larval cuticle proteins while IgE-binding to tropomyosin or arginine kinase was hardly significant [25]. Accordingly, Scala et al. reported a subset of individuals (5.3% of all participants) sensitized to insect proteins without detectable IgE-binding to any crustacean/mollusc panallergens [27]. Thus, tropomyosin, a muscle protein, and larval cuticle proteins, which bind to chitin, present different sensitization capacities in their respective shrimp and YM food matrices. The route of exposure to the allergens could have been additionally determinant for the primary sensitization to YM observed in breeders who were simultaneously exposed by ingestion, skin contact and inhalation to YM proteins, with each route being potentially sensitizing [25,46].

## CROSS- AND DE NOVO SENSITIZATION TO LEGUME PROTEINS

Because they are rich in protein with a low cost of production and are considered more environmentally friendly, legumes are increasingly consumed, not only as legumes, but also as protein isolates included in highly processed plant-based products [47,48]. Currently, only peanut, lupin and soybean are mandatory labeling allergens in the EU but case reports of allergies to other legumes such as pea, lentil, chickpea and beans are accumulating [7,49]. Until now, allergy to legumes was mostly investigated in patients suffering from peanut allergy and thereby legume allergies were often considered as the mere result of cross-reactivity with peanut allergens. Peanut allergy is generally due to an IgE-sensitization to seed storage proteins including the most potent peanut allergens: the 2S albumins Ara h 2 and Ara h 6 [50]. In addition, peanut-allergic patients are sensitized to the 7S (vicilin-type) and 11S (legumin-type) globulins but their elicitation potency is much lower than that of 2S-albumins [41]. Co- and/or cross-sensitization between legumes is frequently observed and is mainly attributed to the 7S/11S globulins, which are generally well identified and characterized in legumes [8–10]. In contrast, 2S-albumins in legumes such as pea, lentil, lupin or beans are either not currently isolated, if actually expressed, or wrongly considered as structural homologs to the archetypical peanut

2S-albumins. Accordingly, peanut-allergic patients are not systematically sensitized to other legumes and co-allergies are rather uncommon in these patients (<17%) [8]. Similarly, in a cohort of 195 peanut-allergic children, 64% were sensitized to at least one other legume, mainly to fenugreek (66%), lentil (42%), soy (40%) and lupin (34%) but the clinical relevance of these cross-sensitizations is much lower since co-allergy to at least one other legume was confirmed in only 17.4% of the population study [9]. On the other hand, patients allergic to pea, lupin, lentil or beans were more frequently co-allergic to peanut (>64%, [8]) and half of allergic reactions to legumes other than to peanut were severe [9]. Though legume allergies remain mostly investigated through the prism of peanut allergy in western countries, studies performed in countries where legumes are more commonly consumed offer a great opportunity to apprehend the impact of the geographic and dietary differences. In Turkey, the annual per capita consumption of chickpea (5.8 kg), lentils (5.6 kg), beans (3.3 kg) and pea (1.1 kg) is much higher than that of peanut (<0.25 kg). In a case series of 87 Turkish children allergic to legumes, the most frequent allergy was to lentil (66%), followed by peanut (61%) then chickpea and pea (28% and 24%, respectively). The highest frequencies of anaphylaxis were caused by lentil (6.4%) and peanut (6.2%). Interestingly, single allergy to peanut was observed in 27 children and to lentils in 9 children while multiple legume allergy without peanut co-allergy was observed in 34 children. When taking into account the level of consumption of peanut and lentil, peanut remained by far the most allergic food protein. However, this study confirmed that legumes other than peanut have the capacity to induce *de novo* sensitization [10]. It should be now investigated whether primary sensitization to lentils results or not in a particular profile of IgE specificity, as observed in patients primarily sensitized to insect proteins.

The development of validated *in silico*, *in vitro* and *in vivo* methods predicting reliably the sensitizing potency of food proteins remains a major challenge, particularly for the integration of food matrices and food processing impacts. In this regard, clinical and postmarket monitoring is of critical importance for reporting emerging food allergens and demonstrating the validity of the premarket assessment [2*].

## SURVEILLANCE OF EMERGING FOOD ALLERGENS

Global surveys comparing the proportion of anaphylaxis triggered by specific foods between
different geographical areas are very scarce and are impaired by the different definitions used worldwide to assign both anaphylaxis and the causative trigger [51]. Nevertheless, local anaphylaxis registers can provide useful data to follow the emergence of food allergens at least at a national level. For example, the French Allergo-Vigilance Network has recorded 2621 cases of food anaphylaxis from 2002 to 2021. While the majority of the recorded anaphylaxis were induced by allergens already on the EU priority list, buckwheat (2.7%), kiwi (1.6%), pea and lentil legumes (1.48%), among others, were reported as emerging allergens since they represent more than 1% of the recorded severe anaphylaxis [52]. The number of anaphylaxis caused by buckwheat, increasingly consumed as a gluten-free alternative to other cereals, is already higher than the number of anaphylaxis caused by some mandatory labeling allergens such as mustard or lupin [17,52]. Data from the European anaphylaxis registry also reported that anaphylaxis to buckwheat was more frequent than anaphylaxis to lupin, while anaphylaxis to mustard was not even reported [53]. Further highlighting the importance of the regional differences of exposure, buckwheat is already considered as a leading cause of food-inducing anaphylaxis in Japan and Korea and is thereby included in their local list of mandatory labeling allergens [54].

Considering the identification of allergens from truly NFs, studies are often limited to a few case reports of allergic reactions and to *in silico* analysis. The latter are performed on available sequenced genomic data or on the proteomic characterization by mass spectrometry of tryptic peptides from the most abundant food proteins [29*]. Thus, recent analysis of food sources such as algae, fungi or spirulina, led to the identification of potential allergens whose IgE-reactivity still needs to be confirmed with specific serum testing. The matter is challenging due to the paucity of these FAs [23]. *Moringa olifeira* leaves are also of interest and are eaten commonly as a vegetable in India, Southeast Asia, and Africa. Recently, five heat-stable IgE-binding proteins were observed by immunoblotting with two sera from allergic patients [21]. Some of them may correspond to the putative allergens identified by D'Auria *et al*. through *in silico* analysis of the leaf proteome but further *in vitro* and *in vivo* assays are required to evaluate the true allergenic potential of this food [22].

## CONCLUSION

With the changing dietary practices, we must anticipate the emergence of novel FAs. Technical and

methodological gaps still preclude a reliable prediction of the allergenic potential of new or modified protein-containing foods. In the meantime, we must strengthen our capacity to monitor the emergence of food allergens, by working closely with allergologists, consumers, patient associations and food safety authorities. In that regard, there is also a need to get a consensus on an acceptable level of allergenic risk that can accommodate the safety of allergic individuals with the possibility to develop and market innovative products that meet the requirements for a more sustainable agrifood system [2*]. Considering that sustainability should not compromise the health of those predisposed to FA, the processing of food sources by various technologies may offer some attractive solutions to reduce food protein allergenic potential.

## Acknowledgements

*None*

## Financial support and sponsorship

Yara Awad was financially supported by the European Union's Horizon 2020 Research and Innovation program under grant agreement no. 101059632 project GIANT LEAPS.

## Conflicts of interest

*There are no conflicts of interest.*

## REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

* of special interest

* of outstanding interest

1. Quintieri L, Nitride C, De Angelis E, et al. Alternative protein sources and novel foods: benefits, food applications and safety issues. *Nutrients* 2023; 15:1509.

2. Crevel RWR, Verhoeckx K, Bøgh KL, et al. Allogenicity assessment of new or

* modified protein-containing food sources and ingredients. *Food Chem Toxicol* 2024; 189:114766.

A comprehensive review that synthesizes the different challenges of allogenicity assessment, including the notion of acceptable risks, the methodological gaps and a generic assessment approach.

3. Jutel M, Agache I, Zemelka-Wiacek M, et al. Nomenclature of allergic diseases and hypersensitivity reactions: adapted to modern needs. *An EAACI position paper. Allergy* 2023; 78:2851–2874.

4. Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. *Allergy* 2023; 78:3057–3076.

5. Bartha I, Almulhem N, Santos AF. Feast for thought: a comprehensive review of food allergy. *J Allergy Clin Immunol* 2024; 153:576–594.

6. FAO, WHO. Risk assessment of food allergens. Part 1: review and validation of codex Alimentarius priority allergen list through risk assessment. *Meeting Report Food Safety and Quality Series No. 14. Rome; 2022.*

7. Abu Risha M, Rick E-M, Plum M, Jappe U. Legume allergens pea, chickpea, lentil, lupine and beyond. *Curr Allergy Asthma Rep* 2024; 24:527–548.

8. Smits M, Verhoeckx K, Knulst A, et al. Co-sensitization between legumes is frequently seen, but variable and not always clinically relevant. *Front Allergy* 2023; 4:1115022.

9. Muller T, Luc A, Adam T, et al. Relevance of sensitization to legumes in peanut-allergic children. *Pediatr Allergy Immunol* 2022; 33:e13846.

10. Soyak Aytekin E, Unsal H, Sahiner UM, et al. IgE mediated legume allergy in east Mediterranean children: a reflection of multiple food allergies. *Pediatr Allergy Immunol* 2022; 33:e13775.
11. Podzhilkova A, Nagl C, Hummel K, et al. Poppy seed allergy: molecular diagnosis and cross-reactivity with tree nuts. J Allergy Clin Immunol Pract 2024; 12:2144–2154.e11.

12. Mattison CP, He Z, Zhang D, et al. Cross-serological reaction of glandless cottonseed proteins to peanut and tree nut allergic IgE. Molecules 2023; 28:1587.

13. Beriziky P, Chernaoui M, Linxe L, et al. Hemp seed: an allergen source with potential cross-reactivity to hazelnut. Food Res Int 2023; 169:112932.

14. Achour J, Guinot M, Guillon B, et al. Sensitization potency of sunflower seed protein in a mouse model: identification of 2S-albumins more allergenic than SFA-8. Mol Nutr Food Res 2021; 65:2100369.

15. Achour J, Reche M, Valbuena T, et al. Sunflower seed allergy: identification of novel 2S-albumins as potential marker allergens. Allergy 2024; 79: 2273–2276.

16. Ballegaard A-SR, Sancho AI, Zhou C, et al. Allergenicity evaluation of quinoa proteins - a study in Brown Norway rats. Food Chem Toxicol 2023; 182: 114118.

17. Farooq M, Wani SM, Mir SA, Naseem Z. An overview of buckwheat allergy: a rare allergenic food. J Food Compos Anal 2023; 123:105616.

18. Bringheli I, Brindisi G, Morelli R, et al. Kiwifruit's allergy in children: what do we know? Nutrients 2023; 15:3030.

19. James CA, Welham S, Rose P. Update on the global prevalence and severity of kiwifruit allergy: a scoping review. Int J Food Sci Technol 2023; 58: 6158–6181.

20. Tuppo L, Alessandri C, Zaccaro L, et al. Isolation, characterization and ige binding of two 2S albumins of pomegranate seeds. Foods 2024; 13:1965.

21. Iddagoda J, Gunasekara P, Handunnetti S, et al. Identification of allergens in *Artocarpus heterophyllus*, *Moringa oleifera*, *Trianthema portulacastrum* and *Syzygium samarangense*. Clin Mol Allergy 2023; 21:6.

22. D'Auria G, Nitride C, Nicolai MA, et al. Identification of allergen encoding sequences in a novel food ingredient from *Moringa oleifera* leaves. Food Chem 2023; 401:134185.

23. Bianco M, Ventura G, Calvano CD, et al. A new paradigm to search for allergenic proteins in novel foods by integrating proteomics analysis and in silico sequence homology prediction: focus on spirulina and chlorella micro-algae. Talanta 2022; 240:123188.

24. Broekman H, Verhoeckx KC, den Hartog Jager CF, et al. Majority of shrimping- allergic patients are allergic to mealworm. J Allergy Clin Immunol 2016; 137:1261–1263.

25. Broekman H, Knulst AC, den Hartog Jager CF, et al. Primary respiratory and food allergy to mealworm. J Allergy Clin Immunol 2017; 140:600–603; e7.

26. Broekman HCHP, Knulst AC, de Jong G, et al. Is mealworm or shrimp allergy indicative for food allergy to insects? Mol Nutr Food Res 2017; 61:1601061.

27. Scala EAD, Villella V, Villalta D, et al. Investigating novel food sensitization: a real-life prevalence study of cricket, locust, and mealworm IgE-reactivity in naïve allergic individuals. J Investig Allergol Clin Immunol 2025; 35:

28. Sharma E, Vitte J. A systematic review of allergen cross-reactivity: Translating basic concepts into clinical relevance. J Allergy Clin Immunol Glob 2024; 3:100230.

A nice comprehensive overview on allergen cross-reactivity.

29. López-Pedrouso M, Lorenzo JM, Alché JD, et al. Advanced proteomic and bioinformatic tools for predictive analysis of allergens in novel foods. Biology (Basel) 2023; 12:714.

A comprehensive review focusing on proteomic and bioinformatic tools to identify putative allergens in novel foods.

30. Li Y, Sackett PW, Nielsen M, et al. NetAllergen, a random forest model integrating MHC-II presentation propensity for improved allergenicity prediction. Bioinform Adv 2023; 3:vbad151.

31. Yang C, Negi SS, Schein CH, et al. AllergenAI: a deep learning model predicting allergenicity based on protein sequence. bioRxiv. 2024;2024.06.22.600179.

32. Mills ENC, Orsenigo F, Salgado D, et al. Novel strategies for predicting allergenicity: development of a ranking method and screening tools to assess the allergy risk of innovative proteins. EFSA Support Publ 2024; 21:8840E.

A nice illustration of the initiatives undertaken to help the developers of in silico methods to refine their outputs.

33. Scaife K, Taylor SL, Pařenicová L, et al. In silico evaluation of the potential allergenicity of a fungal biomass from *Rhizomucor pusillus* for use as a novel food ingredient. Regul Toxicol Pharmacol 2024; 150:105629.

34. Foo ACY, Mueller GA. Abundance and stability as common properties of allergens. Front Allergy 2021; 2:769728.

35. Krutz NL, Kimber I, Winget J, et al. Application of AllerCatPro 2.0 for protein safety assessments of consumer products. Front Allergy 2023; 4:1209495.

36. Yang J, Zhou S, Kuang H, et al. Edible insects as ingredients in food products: nutrition, functional properties, allergenicity of insect proteins, and processing modifications. Crit Rev Food Sci Nutr 2023; 64:10361–10383.

37. Zhou E, Li Q, Zhu D, et al. Characterization of physicochemical and immunogenic properties of allergenic proteins altered by food processing: a review. Food Sci Hum Wellness 2024; 13:1135–1151.

38. Castan L, Bøgh KL, Maryniak NZ, et al. Overview of in vivo and ex vivo endpoints in murine food allergy models: suitable for evaluation of the sensitizing capacity of novel proteins? Allergy 2020; 75:289–301.

39. Dijk W, Villa C, Benede S, et al. Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization. Compr Rev Food Sci Food Saf 2023; 22:971–1005.

An interesting review on the critical features that should be considered for any in vitro model to study epithelial protein transport in the frame of the Adverse Outcome Pathway for allergen sensitization.

40. Morrocchi E, van Haren S, Palma P, Levy O. Modeling human immune responses to vaccination in vitro. Trends Immunol 2024; 45:32–47.

41. Hazebrouck S, Canon N, Dreskin SC. The effector function of allergens. Front Allergy 2022; 3:818732.

42. EFSA Panel on Nutrition, Novel Foods and Food Allergens, Turck D, Castenmiller J, et al. Safety of frozen and dried formulations from migratory locust (Locusta migratoria) as a novel food pursuant to regulation (EU) 2015/2283. EFSA J. 2021;19:e06667.

43. EFSA Panel on Nutrition, Novel Foods and Food Allergens, Turck D, Bohn T, et al. Safety of frozen and dried formulations from whole house crickets (*Acheta domesticus*) as a Novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021;19:e06779.

44. EFSA Panel on Nutrition, Novel Foods and Food Allergens, Turck D, Castenmiller J, et al. Safety of dried yellow mealworm (*Tenebrio molitor larva*) as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021;19:e06343.

45. EFSA Panel on Nutrition, Novel Foods and Food Allergens, Turck D, Bohn T, et al. Safety of frozen and freeze-dried formulations of the lesser mealworm (*Alphitobius diaperinus larva*) as a Novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2022;20:e07325.

46. Ganseman E, Goossens J, Blanter M, et al. Frequent allergic sensitization to farmed edible insects in exposed employees. J Allergy Clin Immunol Pract 2023; 11:3732–3741; e10.

47. Jappe U. Vegan diet—alternative protein sources as potential allergy risk. Allergo J Int 2023; 32:251–257.

48. Präger L, Simon JC, Treudler R. Food allergy – new risks through vegan diet? Overview of new allergen sources and current data on the potential risk of anaphylaxis. J Dtsch Dermatol Ges 2023; 21:1308–1313.

49. Abi-Melhem R, Hassoun Y. Is pea our hidden allergen? An American pediatric case series. J Allergy Clin Immunol Global 2023; 2:100090.

50. Hazebrouck S, Patil SU, Guillon B, et al. Immunodominant conformational and linear IgE epitopes lie in a single segment of Ara h 2. J Allergy Clin Immunol 2022; 150:131–139.

51. Baseggio Conrado A, Patel N, Turner PJ. Global patterns in anaphylaxis due to specific foods: a systematic review. J Allergy Clin Immunol 2021; 148: 1515–1525; e3.

52. Sabouraud-Leclerc D, Tscheiller S, Liabeuf V, Renaudin J-M. Emerging allergens: data from the French Allergo Vigilance Network®. Cahiers Nutr Diétet 2023; 58:190–201.

53. Dölle-Bierke S, Höfer V, Francuzik W, et al. Food-induced anaphylaxis: data from the european anaphylaxis registry. J Allergy Clin Immunol Pract 2023; 11:2069–2079; e7.

54. Jeong KY, Park J-W. Allergens of regional importance in Korea. Front Allergy 2021; 2:652275.