The Effect of Bacille Calmette-Guérin Vaccine Strain and Route of Administration on Induced Immune Responses in Vaccinated Infants

Vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) has variable efficacy in preventing tuberculosis. Both BCG strain and route of administration have been implicated in determining efficacy; however, these variables are not considered in current clinical recommendations for vaccine choice. We eval­ uated antigen-specific immunity after percutaneous or intradermal administration of Japanese BCG or intra­ dermal administration of Danish BCG. Ten weeks after vaccination of neonates, percutaneous Japanese BCG had induced significantly higher frequencies of BCG-specific interferon-y-producing CD4+ and CD8+ T cells in BCG-stimulated whole blood than did intradermal Danish BCG. Similarly, percutaneous vaccination with Japanese BCG resulted in significantly greater secretion of the T helper I-type cytokines interferon-y, tumor necrosis factor-a, and interleukin-2; significantly lower secretion of the T helper 2-type cytokine interleukin­ 4; and greater CD4+ and CD8+ T cell proliferation. Thus, BCG strain and route of neonatal vaccination confer different levels of immune activation, which may affect the efficacy of the vaccine.