Correlation between BCG genomics and protective efficacy

Between the derivation of bacille Calmette-Guerin (BCG) vaccine in 1921 and the lyophilization of BCG daughter strains in the 1960s, a number of clini cal trials were performed looking at the protective efficacy of BCG vaccina tion against tuberculosis. These trials differed from one another in a numb er of ways: they employed different methodologies for delivering the vaccin e and interpreting outcomes; they mere performed on populations with differ ent genetic backgrounds and different levels of exposure to environmental M ycobacteria; and, finally, they used different BCG vaccine strains, The res ults of these trials were estimates of protective efficacy against pulmonar y tuberculosis ranging from about 80% to nil. Because of the differences in outcomes and confounding variables, it is difficult to conclude whether di fferences in interventions alone may have contributed to the remarkably var iable results. Analysis of BCG vaccines used in clinical trials suggests a trend towards decreasing efficacy with increased passage in the laboratory; however, trials that used relatively "older" BCG strains mere generally pe rformed at different sites than trials which used "younger" BCG strains. Ge nomic analysis of BCG vaccines demonstrates that during the half-century of ongoing passage of BCC vaccines in vitro there have been numerous genetic changes, comprising single nucleotide polymorphisms, duplications and delet ions. The impact of these changes in the BCG genome on the protective effic acy observed in field trials remains to be determined.