A Predictive Equation for the Primary Immune Response of Mice to Adsorbed Tetanus Toxoid As a Function of Dose of Antigen and Dose of Adjuvant

Abstract

Abstract Of all the adjuvants used in experimental immunology, the insoluble aluminum compounds comprise the only type permitted in human immunization. They confer a 3- to 10-fold higher primary immune response to the usual protein antigens over that available from the plain fluid state, and such priming enhances the secondary response 20- to 40-fold. Immunologists have long been interested in this more complex dose-response relationship with two independent variables, dose of antigen interacting with dose of adjuvant. Applying the data of a human field trial by using four preparations of AIPO4-adsorbed tetanus toxoid with different antigen-adjuvant ratios, the author previously derived an equation that predicted the mean primary serum antitoxin response of subject groups from the dose of antigen and adjuvant injected. The present paper demonstrates the fit of this equation, with the constant terms changed, to the published data of another investigator who used mice to test 14 adsorbed tetanus toxoid preparations differing in antigen-adjuvant ratio. The probit-survival primary responses of the mice were predicted with reasonable accuracy for all 14 preparations by entering the dose of antigen and of adjuvant of each into the equation. The implications for biologic standardization and for the mechanism of the primary immune response are discussed.