The early primary immune response to absorbed tetanus toxoid in man: A study of the influence of antigen concentration, carrier concentration, and sequence of dosage on the rate, extent, and persistence of the immune response to one and to two doses of toxoid.

A quantitative study was performed to determine the effect of toxoid concentration and aluminium salt concentration on the primary immune response (PIR) and the secondary response induced by tetanus toxoid in human volunteers. Four toxoid preparations having 5-fold differences in toxoid concentration, aluminium salt concentration, or both, were administered to four comparable groups of human volunteers. Antitoxin titres in the serum of each volunteer were determined at intervals. The PIR was found to be a function of the antigen concentration, the mineral concentration, and the interaction of both. The secondary response was a function of the antigen concentration; increase in mineral adjuvant concentration had no significant effect. The data suggested that the higher the post-secondary response, the slower the rate of decline over the ensuing 10 months. The distribution of primary responses at day 28 tended to be bimodal. The response to the best preparation suggested that a single-dose toxoid might be developed to immunize populations that may be difficult to retrieve for multiple injections.