Literature review in support of adjuvanticity/immunogenicity assessment of proteins
The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.
Based on the risk assessment of genetically modified plants, according to Implementing Regulation (EU) No 503/201321 “In cases when known functional aspects of the newly expressed protein or structural similarity to known strong adjuvants may indicate possible adjuvant activity, the applicant shall assess the possible role of these proteins as adjuvants”. To further investigate the topic, an EFSA procurement was launched requesting a comprehensive literature review and critically appraisal on adjuvanticity and immunogenicity of proteins. A systematic literature search and critical review was performed, identifying 299 relevant publications. From the evaluation of the relevant literature emerged that: i) a clear classification of adjuvant and immunogens of proteins cannot be done; ii) structural features able to modulate adjuvanticity and immunogenicity are mainly ascribed to therapeutic proteins and in the context of allergenicity and cross‐reactivity; iii) factors affecting the propensity of a protein to stimulate immune response are aggregation, thermal processing, digestion, food matrix, among others; iv) different proteins are described to have immunomodulatory effects; v) risk assessment of adjuvant and immunogenic behaviour of proteins requires specific methodologies that can be adapted from other fields; vi) adjuvanticity and immunogenicity of Cry proteins in certain experimental conditions seems plausible but due to low dosage, oral route of administration, food and feed processing and digestion, it is unlikely to emerge as a safety issue in food and feed; vii) eliciting an immune response is a very complex matter as the body responds to immune offence by inducing many processes. Based on these considerations, it is expected that the availability of new humanized animal models and the possibility to deploy artificial intelligent systems on the vastity of human data will become a general direction aiming to help answering specific questions relating to the immune systems, including the adjuvanticity and immunogenicity of food/feed proteins.