The induction of mucosal immune responses is particularly important fo
r protection against diseases for which entry and pathogenesis are cle
arly related to the mucosal system, such as salmonellosis, AIDS or tub
erculosis. We investigated the immune responses in guinea-pigs vaccina
ted by BCG via the respiratory compared to the intradermal route. The
results demonstrate that the aerogenic BCG induced a better activation
of broncho-alveolar macrophages and a substantially improved protecti
ve effect against a virulent challenge with Mycobacterium tuberculosis
. We also used a DNA recombinant BCG expressing LacZ gene to investiga
te the influence of various routes of administration on the immunogeni
city of the beta-galactosidase, a foreign antigen expressed by the Lac
Z-BCG recombinant. Thus, lymph-node proliferative responses, delayed t
ype hypersensitivity and antibody responses specific for beta-galactos
idase can be produced in guinea-pigs immunized orally, respiratorily a
nd intradermally. The respiratory and especially the oral route of adm
inistration produced higher mucosal and systemic immune responses comp
ared with the intradermal route of immunization. Moreover, the oral im
munization of mice with recombinant BCG induced IgA responses which ca
n be detected both in sera and in intestinal secretions. In conclusion
, BCG recombinants may be of potential use as an adjuvant vaccine.