1. Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development.
- Author
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Baldrick P, Hutchings JW, Heath MD, and Skinner MA
- Subjects
- Animals, CHO Cells, Cricetulus, Female, Lipid A toxicity, Male, Mutagenicity Tests, Rabbits, Rats, Wistar, Rhinitis, Allergic, Seasonal therapy, Salmonella typhimurium drug effects, Salmonella typhimurium growth & development, Skin drug effects, Adjuvants, Immunologic toxicity, Betula immunology, Immunotherapy adverse effects, Lipid A analogs & derivatives, Pollen immunology, Tyrosine toxicity
- Abstract
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., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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