Intradermal injections of
MER-BCG 0.1 mg or 0.2 mg at each of 10 multiple sites, led to local
granuloma formation. The nodules reached approximately 10 mm in diameter, ulcerated and were accompanied by granulomatous changes in the regional lymph nodes. Six or twelve successive treatments (each including 10
injections) at 4 week intervals produced the same histopathological lesions but no changes in hematological and blood chemical parameters or general morphology and no changes in general condition with exception of occasional
weight loss in a few animals. Injection with 0.01 or 0.001 mg/site produced similar, though less severe, skin lesions but no changes in the draining lymph nodes. The immunogenicity of
MER-BCG was characterized by
granuloma formation, a positive skin response to old
tuberculin, and a positive lymphocyte transformation to
PPD tuberculin, thus indicating stimulation of cell-mediated immune responses. However, there was a decreased responsiveness to PHA and
PPD with continuing treatment with
MER-BCG. The decreased responsiveness and accumulation of numerous depots of
antigen would suggest an "immunologic
paralysis" contraindicating the administration of excessive amounts of
MER-BCG during
immunotherapy. A specific humoral response to the administration of
MER-BCG was not detected, but an
MER-BCG dose independent decrease in
albumin associated with a non-specific, dose related elevation in serum
IgG was observed.