title: A case for a neonatal, low-dose BCG vaccination trial.
abstract: The rational design of a successful vaccination strategy against tuberculosis requires certain kinds of information and must take account of several considerations: (i) the nature of the immune response that protects the large majority of individuals infected by Mycobacterium tuberculosis, designated as healthy contacts, must be defined and distinguished from that in tuberculosis patients, whose immune system must have failed; (ii) the vaccination 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 M. tuberculosis; (iii) the strategy must incorporate a mechanism for ensuring that the effectiveness of this priming is not abrogated by exposure to environmental mycobacteria; and (iv) the strategy must take account of the fact that the vaccinated population is genetically heterogeneous, and that individuals will therefore respond variably to most standard vaccination protocols. We describe a tentative proposal for how these interrelated problems might be solved and discuss predictions of this tentative vaccination strategy. Critical testing of the neonatal, low-dose BCG vaccination strategy can only be achieved by a field trial and we outline the considerations underlying this proposal.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Bretscher
authors.forename: J
authors.initials: J
authors.lastname: Menon
authors.forename: C
authors.initials: C
authors.lastname: Power
authors.forename: J
authors.initials: J
authors.lastname: Uzonna
authors.forename: G
authors.initials: G
authors.lastname: Wei
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001500:BCG Vaccine / Q000008:administration & dosage*; D002986:Clinical Trials as Topic / Q000379:methods; D004195:Disease Models, Animal; D005828:Genetics, Population; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007156:Immunologic Memory; D007231:Infant, Newborn; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
chemical_list: D001500:BCG Vaccine