The potential of Lactobacillus as a carrier for oral immunization: development and preliminary characterization of vector systems for targeted delivery of antigens

Abstract

Oral administration of lactobacilli evokes mucosal and systemic immune responses against epitopes associated with these organisms (Gerritse et al., 1990, 1991). The adjuvant function of different Lactobacillus species was investigated under the conditions of intraperitoneal (i.p.) injection or oral administration. After i.p. injection of trinitrophenylated chicken gamma-globulin, high DTH responses were observed with Lactobacillus casei and Lactobacillus plantarum, but low responses with Lactobacillus fermentum and Lactobacillus delbrueckii subsp. bulgaricus. In different experimental model systems L. casei and L. plantarum consistently showed significant adjuvanticity. A series of expression and expression-secretion vectors containing the strong constitutive promoter of the L. casei L-ldh gene or the regulatable promoter of the Lactobacillus amylovorus amy gene (Pouwels and Leer, 1995) was used for the intracellular, extracellular and surface-bound expression of an influenza virus antigenic determinant fused to Escherichia coli beta-glucuronidase. Intracellular expression of the fusion protein amounted to 1-2% of total soluble protein. Lactobacilli synthesizing the fusion protein intracellularly evoked an oral immune response after subcutaneous priming.