EXPERIMENTAL studies of vaccination, allergy, and immunity in tuberculosis. I. Design for a research programme.

With the growing popularity of BCG vaccination in tuberculosis control programmes, the tuberculin test has become a widely accepted means of determining the success of vaccination, despite persistent disagreement in scientific circles about the relation between skin sensitivity to tuberculin and acquired resistance to tuberculosis. With little hope today of solving the allergy-immunity problem by studies on human beings, and because of the urgent practical need for guide-lines for international mass BCG campaigns, a research programme in laboratory animals has been patterned on extensive studies of BCG vaccination and post-vaccination allergy in school-children.The programme, composed of a series of separate but interrelated projects, is not primarily concerned with the academic intricacies of the allergy-immunity problem. Rather, it has more directly practical objectives. First, to reproduce as nearly as possible in animals what is now being done in vaccination programmes in human beings, in order to compare, in the two species, the responses that are readily observable in man. Secondly, by challenging the vaccinated animals with virulent organisms, to study the association between those responses and resistance to virulent infection. Finally, from the results so obtained, to determine whether and to what extent some observable response to vaccination can be used (by analogy) as a practical guide to the successful vaccination of man.The experimental design takes into account variation in the animals, the vaccines, the challenge infection, and other pertinent factors. Large numbers of animals and randomization procedures have been necessary to ensure that all kinds of variation-biological, sampling, observer errors, etc.-are reduced to a minimum and distributed by chance among the various experimental groups. Observations and techniques common to the projects so far undertaken in the programme are described in the last section of the paper.