Strain Variation in the IgG1 Antibody Response to Proteins Administered Intranasally in the Mouse

Abstract

Proteins, including enzymes, have the potential to behave as respiratory allergens. In consequence, guinea pig methods have been developed which permit an assessment to be made of their respiratory allergenic/antigenic potential relative to an appropriate reference substance. Recently, a murine model, the mouse intranasal test (MINT) has been proposed as a potential alternative. However, to be of value, the new method should give a rank order of relative potency for a range of proteins which correlates with that found in guinea pig models and in human experience. Using the mouse strain recommended for the MINT, BDF1, in an extensive intralaboratory assessment, the relative potency of several of the eight proteins used was at variance with that expected from the historic data. Where genetic factors are important, as in the assessment of antigenicity, the rank order for a range of proteins in a particular inbred or F1 hybrid strain may not reflect that in humans. To examine whether the earlier observations were a strain rather than a species dependent phenomenon, five proteins of varying antigenic potency previously tested using the BDF1 strain were selected and tested using the MINT protocol in BALB/c, CBA/Ca and CB6F1 inbred/F1 hybrid strains, as well as in the outbred Swiss S strain. The results clearly indicated that the relative potency of the proteins was dependent on the mouse strain used and thus with haplotype. When assessed against the standard reference enzyme, Alcalase (a process used for the establishment of occupational exposure guidelines), the rank order was strain dependent and results from none of the mouse strains would have led to similar conclusions to those derived from existing models and the human epidemiological data. Based on the presently available information, it is not possible to be certain that any mouse model reliant on the responsiveness of a particular strain (including the MINT) might not lead to an incorrect estimation of respiratory antigenic and thus allergenic potency. In consequence, the MINT may not be viable as a model for the assessment of the relative ability of proteins to behave as respiratory allergens.