A battery of genotoxicity studies with an allergy vaccine adjuvanted with monophosphoryl lipid A (MPL®) for the treatment of grass pollen allergy

Abstract

The allergy vaccine Pollinex® Quattro Grass, developed for the prevention/relief of allergic symptoms caused by grass pollen in adults and children, contains extracts of 12 grass pollens and rye cereal (all chemically modified by glutaraldehyde), adsorbed onto L-tyrosine with addition of the immunostimulatory adjuvant monophosphoryl lipid A (MPL®). This paper represents the first publication on genetic toxicology data for such a vaccine. An Ames test using five strains of Salmonella typhimurium at concentrations up to 2000 standardized units (SU) per plate in the absence (-) and presence (+) of metabolic activation (rat liver S9) showed negative results, as did treatment - S9 in the mouse lymphoma assay (MLA). However, a reproducible positive response was noted in the MLA + S9, which could not be attributed to extreme culture conditions, but may have been an artefact of the exogenous metabolizing system. Up to 60% false positive results are reported for the MLA with noncarcinogens. Hence, in vivo genotoxicity studies were conducted. These further assessments comprised a rat bone marrow micronucleus test following subcutaneous (s.c.) doses of 10 000, 20 000 or 40 000 SU kg⁻¹ per day for 2 days, and a comet assay in liver and kidney cells from rats treated with Pollinex® Quattro Grass at 20 000 or 40 000 SU kg⁻¹ per day s.c. for 2 days. Plasma analysis showed evidence of systemic antibodies to Pollinex® Quattro Grass immunogens, but the exposure levels could not be quantified. No evidence of genotoxicity was observed in either of the in vivo studies. Overall, the genotoxicity test results supported safe clinical use of Pollinex® Quattro Grass.