Mucosal Immune Responses and Protection against Tetanus Toxin after Intranasal Immunization with RecombinantLactobacillus plantarum

Abstract

The use of live microorganisms as an antigen delivery system is an effective means to elicit local immune responses and thus represents a promising strategy for mucosal vaccination. In this respect, lactic acid bacteria represent an original and attractive approach, as they are safe organisms that are used as food starters and probiotics. To determine whether an immune response could be elicited by intranasal delivery of recombinant lactobacilli, a Lactobacillus plantarum strain of human origin (NCIMB8826) was selected as the expression host. Cytoplasmic production of the 47-kDa fragment C of tetanus toxin (TTFC) was achieved at different levels depending on the plasmid construct. All recombinant strains proved to be immunogenic by the intranasal route in mice and able to elicit very high systemic immunoglobulin G (IgG1, IgG2b, and IgG2a) responses which correlated to the antigen dose. No significant differences in enzyme-linked immunosorbent assay IgG titers were observed when mice were immunized with live or mitomycin C-treated recombinant lactobacilli. Nevertheless, protection against the lethal effect of tetanus toxin was obtained only with the strains producing the highest dose of antigen and was greater following immunization with live bacteria. Significant TTFC-specific mucosal IgA responses were measured in bronchoalveolar lavage fluids, and antigen-specific T-cell responses were detected in cervical lymph nodes, both responses being higher in mice receiving a double dose of bacteria (at a 24-h interval) at each administration. These results demonstrate that recombinant lactobacilli can induce specific humoral (protective) and mucosal antibodies and cellular immune response against protective antigens upon nasal administration.

Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization

“…Recent studies have highlighted the effects of probiotic bacteria on immune competent cells (3,4,(24)(25)(26). In the present study, we investigated the adjuvanticity of three Lactobacillus species on immature human MDCs and showed that Lactobacillus cells induced activation and maturation of MDCs.…”

Mucosal Vaccine Made from Live, RecombinantLactococcus lactisProtects Mice against Pharyngeal Infection withStreptococcus pyogenes

“…The only approved mucosal vaccines are pathogens (49), some of which may pose a risk of infection, particularly to children or immunocompromised individuals (36,39,46). Therefore, recent efforts to develop mucosal vaccine delivery systems have included ones that are not pathogenic, such as liposomes or microparticles (10,50), commensal bacteria (19,20,32,34,39,45,46), or noninvasive, noncommensal bacteria (11,18,31,42).…”

Genes involved in obesity: Adipocytes, brain and microflora

“…Finally, probiotics, thanks to their GRAS characteristics associated with their high resistance to the gastric barrier, have been genetically engineered as tools for the delivery of antigens or therapeutic molecules (Robinson et al, 1997;Steidler et al, 2000;Grangette et al, 2001). Nevertheless and obviously, there are many scientific, political and social barriers to allow the introduction of such genetically modified organisms.…”