Safety evaluation of a glutaraldehyde modified tyrosine adsorbed housedust mite extract containing monophosphoryl lipid A (MPL (R)) adjuvant: a new allergy vaccine for dust mite allergy

摘要

A new allergy vaccine is currently under clinical evaluation for the prevention or relief of symptoms caused by specific housedust mites. It consists of a 50:50 mixture of the mite Dermatophagoides pteronyssinus and D. farinae protein derived from aqueous extracts of the mites which is chemically modified by glutaraldehyde and adsorbed onto L-tyrosine with addition of the immunostimulatory adjuvant, monophosphoryl lipid A (MPL (R)) "Polymite". A specific preclinical safety testing strategy was developed to support clinical use and comprised single and repeat dose toxicity, reproduction toxicity and local tolerance studies. Dose levels of up to 0.5 ml for the mouse and up to 1 ml for both the rat and the rabbit were used. Overall, the product was shown to produce no toxicological findings of significance at levels greatly in excess to those proposed for clinical use. A not unexpected, but relatively minor, immunostimulatory effect was seen following repeated dosing (once weekly for 13 weeks) at 1 ml per rat; the Polymite formulation also resulted in injection site reaction which can largely be attributed to the presence of tyrosine. No reproduction toxicity was found.