Boosting of cellular immunity against Mycobacterium tuberculosis and modulation of skin cytokine responses in healthy human volunteers by Mycobacterium bovis BCG substrain Moreau Rio de Janeiro oral vaccine

Abstract

Oral immunization of healthy adults with 10(7) CFU BCG Moreau Rio de Janeiro was well tolerated and significantly boosted gamma interferon responses to purified protein derivative, Ag85, and MPB70 from previous childhood intradermal BCG immunization. Oral BCG offers the possibility of a needle-free tuberculosis vaccine and of boosting the protective immunity from intradermal tuberculosis vaccines.

FIG. 1.

Frequency of PBMCs secreting IFN-γ in response to mycobacterial antigens at primary protocol time points after oral immunization with BCG. Values are frequency of IFN-γ-secreting cells per 10⁶ PBMCs (corrected for background activity in wells without antigen) for 13 subjects with complete data sets at primary protocol time points after oral immunization. Columns are group means. Error bars are standard errors of the means. Differences from day 0 were analyzed using GraphPad Prism by repeated-measures one-way analysis of variance and corrected by Dunnett's test for multiple comparisons.

FIG. 2.

Relative quantity of cytokine mRNA in skin biopsies of Heaf tests before and after oral liquid BCG vaccine. Values indicate relative amounts of cytokine RNA extracted from skin biopsies taken 7 days after a standard tuberculin Heaf test, either before oral BCG immunization or 1 month after. Subject V039, diamonds; subject V040, circles; subject V041, squares; subject V043, triangles. ND, not detected. All cytokine mRNAs were assessed relative to a standard control RNA except V039 IFN-γ, which used a different control RNA (indicated by dotted line). No preimmunization results on V041 for IL-1α and -β, IL-2, IL-12p40, and IL-15 were available due to insufficient sample. The y axes are plotted on a logarithmic scale.