Evaluation of the protective potency of new tuberculosis vaccines.

Animal models used to evaluate the relative protective potency of a panel of tuberculosis vaccines have yielded dissimilar data. Moreover, it is not known which animal model predicts the protective potency of vaccines for humans. Accordingly, animal models should be developed on the basis of an understanding of the key events in the pathogenesis of tuberculosis in humans. Vaccines such as bacille Calmette-Guérin (BCG) appear to protect against tuberculosis by inhibiting the bacillemic phase of primary infection with virulent tubercle bacilli; therefore, such vaccines can be expected to provide protection against tuberculosis developing via the endogenous reactivation pathway but not against disease developing via the exogenous reinfection pathway. To protect against disease developing by the latter pathway, it would appear that new vaccines produced by recombinant DNA technology or through use of monoclonal antibody would have to inhibit the implantation of bacilli at the portal of entry in the lungs. Experience with BCG vaccine indicates that factors other than the inherent potency of the vaccine play a decisive role in the outcome of vaccine trials in humans. These same factors will probably influence field trials of any new generation of tuberculosis vaccines.