Vaccine-Induced Subcutaneous Granulomas in Goats Reflect Differences in Host-Mycobacterium Interactions between BCG- and Recombinant BCG-Derivative Vaccines

Tuberculous granulomas are highly dynamic structures reflecting the complex host-mycobacterium interactions. The objective of this study was to compare granuloma development at the site of vaccination with BCG and its recombinant derivatives in goats. To characterize the host response, epithelioid cells, multinucleated giant cells (MNGC), T cell subsets, B cells, plasma cells, dendritic cells and mycobacterial antigen were labelled by immunohistochemistry, and lipids and acid-fast bacteria (AFB) were labelled by specific staining. Granulomas with central caseous necrosis developed at the injection site of most goats though lesion size and extent of necrosis differed between vaccine strains. CD4(+) T and B cells were more scarce and CD8(+) cells were more numerous in granulomas induced by recombinant derivatives compared to their parental BCG strain. Further, the numbers of MNGCs and cells with lipid bodies were markedly lower in groups administered with recombinant BCG strains. Microscopic detection of AFB and mycobacterial antigen was rather frequent in the area of central necrosis, however, the isolation of bacteria in culture was rarely successful. In summary, BCG and its recombinant derivatives induced reproducibly subcutaneous caseous granulomas in goats that can be easily monitored and surgically removed for further studies. The granulomas reflected the genetic modifications of the recombinant BCG-derivatives and are therefore suitable models to compare reactions to different mycobacteria or TB vaccines.

Automated summary

This study compares the development of tuberculous granulomas at the site of BCG vaccination and its recombinant derivatives in goats. The results show that granulomas with central caseous necrosis are induced by both BCG and its recombinant derivatives, although the size and extent of necrosis differ between vaccine strains. The recombinant derivatives induce fewer CD4(+) T and B cells and more CD8(+) cells in the granulomas compared to the parental BCG strain. Furthermore, the numbers of multinucleated giant cells (MNGCs) and cells with lipid bodies are significantly lower in groups administered with the recombinant BCG strains. These findings suggest that the granulomas induced by BCG and its recombinant derivatives in goats can serve as suitable models to compare reactions to different mycobacteria or tuberculosis vaccines.