Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development.
PQ Birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. It consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to L-tyrosine in its microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). A nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity studies (bacterial reverse mutation and Chinese hamster ovary micronucleus assays), a rat repeat dose toxicology study and a rabbit local tolerance study. No safety findings of concern were found. Thus, no evidence of genotoxicity was found. Relatively minor, immunostimulatory effects were seen following repeated subcutaneous dosing (once every 2 weeks for 13 weeks) as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased albumin/globulin [A/G] ratio) and increased fibrinogen, as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL® and/or the presence of L-tyrosine within the adjuvanted vaccine. Similar dose site inflammatory changes to the injected formulation were also noted in the rabbit local tolerance study.
['Baldrick|Paul|P|', 'Hutchings|James W|JW|', 'Heath|Matthew D|MD|', 'Skinner|Murray A|MA|']
D000276:Adjuvants, Immunologic D000818:Animals D029662:Betula D016466:CHO Cells D003412:Cricetulus D005260:Female D007167:Immunotherapy D008050:Lipid A D008297:Male D009152:Mutagenicity Tests D011058:Pollen D011817:Rabbits D017208:Rats, Wistar D006255:Rhinitis, Allergic, Seasonal D012486:Salmonella typhimurium D012867:Skin D014443:Tyrosine
PQ birch Birch pollen Genotoxicity Toxicology study Allergy vaccine