Comparison of the efficacy of intranasal versus subcutaneous bacillus calmette-guerin (BCG) vaccination against challenge with virulent Mycobacterium tuberculosis

We compared intranasal versus subcutaneous BCG vaccine induced protective efficacy against challenge with virulent Mycobacterium tuberculosis (M. tb). We also determine the early and late cellular events after intranasal and subcutaneous BCG vaccination. We found that intranasal vaccination induces better protection than subcutaneous vaccination against virulent M. tb infection. Both intranasal and subcutaneous BCG vaccination routes induced early IFN-gamma production by NK cells. Intranasal vaccination but not subcutaneous vaccination induced early IL-15 and IL-23 mRNA expression by CD11C+ splenic and mediastinal lymph node dendritic cells respectively and IL-17 production by spleen and mediastinal lymph node (MLN) cells. In contrast, one month after subcutaneous vaccination, peripheral lymph node (PLN) cells produced higher amounts of IL-17 in response to gamma-irradiated M. tb H37Rv. Our results suggest that early immune cell interaction through IFN-gamma production by NK cells, IL-15 and IL-23 production by splenic and mediastinal lymph node dendritic cells respectively and IL-17 production by T-cells may shape subsequent protective immune responses in intranasal and subcutaneous vaccinated mice.