The effect of heterologous immunity upon the apparent efficacy of (e.g. BCG) vaccines.

Exposure of populations to microbes which share antigens with pathogens can influence the apparent efficacy of vaccines. This may explain the great variation (from below 0 to 80%) observed in protection by Bacillus Calmette Guérin (BCG) against tuberculosis. This paper explores three models for the effect of such heterologous immunity, and demonstrates that: (a) if the immune responses to the microbial antigens in nature and in the vaccines differ qualitatively, there will be no effect on observed efficacy; (b) if the immune responses differ only quantitatively, the observed vaccine efficacy will be reduced, and it will be minimal when vaccine-induced and heterologous protection are of similar magnitude; and (c) if the heterologous exposure can block the vaccine action, then observed efficacy will be reduced and may even appear negative. These results provide important guidance for the interpretation of BCG's utility and for the development and evaluation of new vaccines, in particular against tuberculosis.