A case for a neonatal, low-dose BCG vaccination trial

The rational design of a successful vaccination strategy against tuberculos is requires certain kinds of information and must take account of several c onsiderations: (i) the nature of the immune response that protects the larg e majority of individuals infected by Mycobacterium tuberculosis, designate d as healthy contacts, must be defined and distinguished from that in tuber culosis patients, whose immune system must have failed; (ii) the vaccinatio n strategy must incorporate a way of priming the immune system to guarantee in all individuals this protective response, normally generated in healthy contacts, upon natural infection by hi. tuberculosis; (iii) the strategy m ust incorporate a mechanism for ensuring that the effectiveness of this pri ming is not abrogated by exposure to environmental mycobacteria; and (iv) t he strategy must take account of the fact that the vaccinated population is genetically heterogeneous, and that individuals will therefore respond var iably to most standard vaccination protocols. We describe a tentative propo sal for how these interrelated problems might be solved and discuss predict ions of this tentative vaccination strategy. Critical testing of the neonat al, low-dose BCG vaccination strategy can only be achieved by a field trial and we outline the considerations underlying this proposal.