- Email: [email protected]
FP 9 Immunotoxicological study in Beluga whales
Abstracts of the 7th Congress of the ISDCI: Session F
131
FP9
IMMUNOTOXICOLOGICAL
STUDY IN BELUGA WHALES
FOURNIER M.‘, DE GUISE S.‘, MARTINEAU D.2,BOILEAU S.‘, BELAND P’, SPEAR, P’, LAPIERRE, P.‘. ‘Universite du Quebec a Montreal, Montreal, (QuCbec), Canada. 2FacultCde medecine vettrinaire, Ste-Hyacinthe (QuCbec), Canada. %stitut National d’Ecotoxicologie du St-Laurent, Montreal, (Quebec), Canada.
Over the last decades, high concentrations of environmental contaminants such as PCBs have been measured in the tissues of many speciesof marine mammals from different part of the world. Even though many deleterious effects of these compounds have been reported inlaboratory animals, the overall risk associated with these contaminants in wild animals is still not clearly understood. However, necropsy of St Lawrence belugas showed numerous severe and disseminated infections with rather mildly pathogenic bacteria. Moreover, 37% of all the tumors reported in cetaceans were observed in St. Lawrence beluga whales. Indeed, both observations suggest immunosuppression. The aim of the study was to determined if contaminants present in fat tissues of belugas might provoke deleterious effect to their immune system if under some circumstances they are released into the circulation. To assesstheir immunotoxic potential, rats were fed for two months on a diet in which the lipids originated from the blubber of either highly polluted St. Lawrence belugas of relatively uncontaminated arctic belugas. Then, multiple immune responses were monitored. Those include phagocytosis, plaque forming cells, oxidative burst, natural killer cells, immunophenotyping and mitogenic assay.The results obtained show that only the humoral response of rats was impaired by the treatment. By combining all these informations, we propose possible mechanisms of action to explain potential long-termconsequences of environmental pollution.
FP 10
MACAQUE ANTI-HUMAN ANTIBODIES: ANALYSIS OF THE HOST RESPONSE TO A THERAPEUTIC HUMANIZED ANTIBODY Elizabeth R. Gore, Danuta J. Herzyk, Sandra D. Griego, Charles B. Davis, Carol Silverman, Peter J. Bugelski and Timothy K. Hart. Departments of Toxicology, Molecular Virology and Host Defense, Drug Metabolism, and Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
Preclinical testing of humanized monoclonal antibodies (hMAb) includes evaluation of antigenicity in the toxicology test species. Single administrations of hMAb to primates generally are not antigenic and the hMAb has a long circulating half-life. Repeated administration of hMAb to primates can result in the generation of anti-hMAb antibodies, a resultant increased rate of hMAb elimination and potential anaphylactoid responses. Generally, the immunodominant antibody response to a hMAb in primates is anti-idiotypic. In the preclinical safety assessmentof a hMAb to respiratory syncytial virus, cynomolgus monkeys raised primarily anti-isotype antibodies following single intravenous or intramuscular administrations. Following repeat administration, a stronger anti-idiotype response was detected, but the anti-isotype remained immunodominant. Monkey antibodies recognized other mono- and polyclonal human IgGs. Analysis of the monkey antibodies revealed that the antigenic epitope(s) were in the Fab fragment of the hMAb and the IgG light and heavy chain constant regions were immunodominant. All monkey anti-hMAbs neutralized binding of hMAb to antigen, but only monkey antibodies expressed following repeat adminstration were neutralizing of the anti-viral effect of the hMAb. Plasma clearance of the hMAb was much more rapid in the presence of monkey antibodies. These fstudiesdemonstrate that single doses of hMAb to monkeys can be antigenic and that a strong anti-isotype response to conserved immunoglobulin domains (vs. murine sequences) is possible.
131
FP9
IMMUNOTOXICOLOGICAL
STUDY IN BELUGA WHALES
FOURNIER M.‘, DE GUISE S.‘, MARTINEAU D.2,BOILEAU S.‘, BELAND P’, SPEAR, P’, LAPIERRE, P.‘. ‘Universite du Quebec a Montreal, Montreal, (QuCbec), Canada. 2FacultCde medecine vettrinaire, Ste-Hyacinthe (QuCbec), Canada. %stitut National d’Ecotoxicologie du St-Laurent, Montreal, (Quebec), Canada.
Over the last decades, high concentrations of environmental contaminants such as PCBs have been measured in the tissues of many speciesof marine mammals from different part of the world. Even though many deleterious effects of these compounds have been reported inlaboratory animals, the overall risk associated with these contaminants in wild animals is still not clearly understood. However, necropsy of St Lawrence belugas showed numerous severe and disseminated infections with rather mildly pathogenic bacteria. Moreover, 37% of all the tumors reported in cetaceans were observed in St. Lawrence beluga whales. Indeed, both observations suggest immunosuppression. The aim of the study was to determined if contaminants present in fat tissues of belugas might provoke deleterious effect to their immune system if under some circumstances they are released into the circulation. To assesstheir immunotoxic potential, rats were fed for two months on a diet in which the lipids originated from the blubber of either highly polluted St. Lawrence belugas of relatively uncontaminated arctic belugas. Then, multiple immune responses were monitored. Those include phagocytosis, plaque forming cells, oxidative burst, natural killer cells, immunophenotyping and mitogenic assay.The results obtained show that only the humoral response of rats was impaired by the treatment. By combining all these informations, we propose possible mechanisms of action to explain potential long-termconsequences of environmental pollution.
FP 10
MACAQUE ANTI-HUMAN ANTIBODIES: ANALYSIS OF THE HOST RESPONSE TO A THERAPEUTIC HUMANIZED ANTIBODY Elizabeth R. Gore, Danuta J. Herzyk, Sandra D. Griego, Charles B. Davis, Carol Silverman, Peter J. Bugelski and Timothy K. Hart. Departments of Toxicology, Molecular Virology and Host Defense, Drug Metabolism, and Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
Preclinical testing of humanized monoclonal antibodies (hMAb) includes evaluation of antigenicity in the toxicology test species. Single administrations of hMAb to primates generally are not antigenic and the hMAb has a long circulating half-life. Repeated administration of hMAb to primates can result in the generation of anti-hMAb antibodies, a resultant increased rate of hMAb elimination and potential anaphylactoid responses. Generally, the immunodominant antibody response to a hMAb in primates is anti-idiotypic. In the preclinical safety assessmentof a hMAb to respiratory syncytial virus, cynomolgus monkeys raised primarily anti-isotype antibodies following single intravenous or intramuscular administrations. Following repeat administration, a stronger anti-idiotype response was detected, but the anti-isotype remained immunodominant. Monkey antibodies recognized other mono- and polyclonal human IgGs. Analysis of the monkey antibodies revealed that the antigenic epitope(s) were in the Fab fragment of the hMAb and the IgG light and heavy chain constant regions were immunodominant. All monkey anti-hMAbs neutralized binding of hMAb to antigen, but only monkey antibodies expressed following repeat adminstration were neutralizing of the anti-viral effect of the hMAb. Plasma clearance of the hMAb was much more rapid in the presence of monkey antibodies. These fstudiesdemonstrate that single doses of hMAb to monkeys can be antigenic and that a strong anti-isotype response to conserved immunoglobulin domains (vs. murine sequences) is possible.