Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15–56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals: a PARC (Partnership for the Assessment of Risk from Chemicals) project

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC)

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals — a PARC (Partnership for the Assessment of Risk from Chemicals) project

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC)

Transfert et métabolisme des hydrocarbures aromatiques polycycliques chez le ruminant laitier

Suite au dépôt des HAP dans l'environnement, le fourrage devient une voie d'exposition potentielle des ruminants. Un système d'élevage herbager engendrerait une exposition du troupeau aux HAP supérieure à celui de type maïs fourrage. L'étude du transfert fourrage-lait chez la vache laitière montre que seuls les composés <5 cycles sont détectés avec des coefficients de transferts apparents de 1 à 30%. L'ingestion de 14-CHAP par des chèvres a révélé un faible transfert vers le lait (phénanthrène 1,5%, pyrène 1,9% et benzo[a]pyrène 0,2%). Leurs caractéristiques et leurs aptitudes à la biotransformation apparaissent comme les facteurs clés de ces mécanismes de transfert. Le métabolisme du phénanthrène étudié en CG-SM influencerait le devenir du composé dans l'animal et les produits d'excrétion. Les OHphénanthrènes, le 1-0Hpyrène et le 2-0Hfluorène ont été identifiés dans le lait de chèvre suite à des apports en HAP suggérant une induction du métabolisme en fonction de la dose administrée.NANCY/VANDOEUVRE-INPL (545472102) / SudocSudocFranceF

Le transfert des micropolluants organiques dans la chaîne alimentaire Etat et perspectives de recherche

Les hydrocarbures aromatiques polycycliques ont récemment défrayé la chronique à plusieurs reprises. Cet article se propose de faire le point sur les propriétés de ces molécules en vue de donner un aperçu des voies pour la recherche d’outils d’évaluation et de gestion des risques liés à ces molécules. De nombreuses molécules peuvent prétendre appartenir à cette famille. Nous traiterons de celles les plus communément impliquées dans les problèmes de sécurité alimentaire, à savoir la famille des dioxines-furanes ou polychloro-dibenzo-paradioxines/furanes (PCDD/F), celle des composés polychlorés biphényles (PCB) et enfin celle des hydrocarbures aromatiques polycycliques (HAP) que nous réserverons dans ce texte aux composés non chlorés

Le transfert des micropolluants organiques dans la chaîne alimentaire Etat et perspectives de recherche

Les hydrocarbures aromatiques polycycliques ont récemment défrayé la chronique à plusieurs reprises. Cet article se propose de faire le point sur les propriétés de ces molécules en vue de donner un aperçu des voies pour la recherche d’outils d’évaluation et de gestion des risques liés à ces molécules. De nombreuses molécules peuvent prétendre appartenir à cette famille. Nous traiterons de celles les plus communément impliquées dans les problèmes de sécurité alimentaire, à savoir la famille des dioxines-furanes ou polychloro-dibenzo-paradioxines/furanes (PCDD/F), celle des composés polychlorés biphényles (PCB) et enfin celle des hydrocarbures aromatiques polycycliques (HAP) que nous réserverons dans ce texte aux composés non chlorés

Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants

International audienceThe incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). In many ways, this expands the classical “Developmental Origins of Health and Disease” paradigm to include exposure to pollutants. This model has been refined over the years to give the current “three-hit” model that considers the individual’s genetic factors as a first “hit.” It has an immediate interaction with the early-life exposome (including persistent organic pollutants) that can be considered to be a second “hit.” Together, these first two “hits” produce a quiescent or latent phenotype, most probably encoded in the epigenome, which has become susceptible to a third environmental “hit” in later life. It is only after the third “hit” that the increased risk of disease symptoms is crystallised. However, if the individual is exposed to a different environment in later life, they would be expected to remain healthy. In this review, we examine the effect of exposure to persistent organic pollutants and particulate matters in early life and the relationship to subsequent neurodevelopmental and neurodegenerative disorders. The roles of those environmental factors which may affect epigenetic DNA methylation and therefore influence normal neurodevelopment are then evaluated

Le transfert des micropolluants organiques dans la chaîne alimentaire Etat et perspectives de recherche

Les hydrocarbures aromatiques polycycliques ont récemment défrayé la chronique à plusieurs reprises. Cet article se propose de faire le point sur les propriétés de ces molécules en vue de donner un aperçu des voies pour la recherche d’outils d’évaluation et de gestion des risques liés à ces molécules. De nombreuses molécules peuvent prétendre appartenir à cette famille. Nous traiterons de celles les plus communément impliquées dans les problèmes de sécurité alimentaire, à savoir la famille des dioxines-furanes ou polychloro-dibenzo-paradioxines/furanes (PCDD/F), celle des composés polychlorés biphényles (PCB) et enfin celle des hydrocarbures aromatiques polycycliques (HAP) que nous réserverons dans ce texte aux composés non chlorés