Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development.

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.

• Authors: Paul Baldrick, James W Hutchings, Matthew D Heath, Murray A Skinner
• Journal: Regulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 108 Pg. 104441 (Nov 2019) ISSN: 1096-0295 [Electronic] Netherlands
• PMID: 31425728 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Adjuvants, Immunologic
• Lipid A
• Tyrosine
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (toxicity)
• Animals
• Betula (immunology)
• CHO Cells
• Cricetulus
• Female
• Immunotherapy (adverse effects)
• Lipid A (analogs & derivatives, toxicity)
• Male
• Mutagenicity Tests
• Pollen (immunology)
• Rabbits
• Rats, Wistar
• Rhinitis, Allergic, Seasonal (therapy)
• Salmonella typhimurium (drug effects, growth & development)
• Skin (drug effects)
• Tyrosine (toxicity)