Tuberculosis Vaccine Conundrum

Science Signaling  02 Oct 2012:
Vol. 5, Issue 244, pp. ec258
DOI: 10.1126/scisignal.2003652

Some children experience severe clinical disease when they are vaccinated against tuberculosis with an attenuated live vaccine that is normally innocuous in humans. Several germline mutations have been identified that account for this susceptibility, and now Bogunovic et al. add another to the list—ISG15. Uncovering this mutation, which is inherited in an autosomal recessive manner, was a surprise because studies with mice deficient in ISG15 showed enhanced susceptibility to some viral, but not bacterial, infections. Nevertheless, patients lacking ISG15 were not able to produce adequate amounts of interferon-γ, a cytokine critical for clearance of the bacteria.

D. Bogunovic, M. Byun, L. A. Durfee, A. Abhyankar, O. Sanal, D. Mansouri, S. Salem, I. Radovanovic, A. V. Grant, P. Adimi, N. Mansouri, S. Okada, V. L. Bryant, X.-F. Kong, A. Kreins, M. Moncada Velez, B. Boisson, S. Khalilzadeh, U. Ozcelik, I. A. Darazam, J. W. Schoggins, C. M. Rice, S. Al-Muhsen, M. Behr, G. Vogt, A. Puel, J. Bustamante, P. Gros, J. M. Huibregtse, L. Abel, S. Boisson-Dupuis, J.-L. Casanova, Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337, 1684–1688 (2012). [Abstract] [Full Text]