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      Oral vaccination of mice against tetanus with recombinant Lactococcus lactis.

      Nature biotechnology
      Administration, Intranasal, Administration, Oral, Animals, Antibodies, Bacterial, blood, Biotechnology, Female, Immunity, Mucosal, Immunoglobulin G, Lactococcus lactis, genetics, immunology, Mice, Mice, Inbred C57BL, Peptide Fragments, Tetanus, prevention & control, Tetanus Toxin, Tetanus Toxoid, administration & dosage, Vaccination, Vaccines, Synthetic

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          Abstract

          To determine whether a protective immune response could be elicited by oral delivery of a recombinant bacterial vaccine, tetanus toxin fragment C (TTFC) was expressed constitutively in Lactococcus lactis and administered orally to C57 BL/6 mice. The antibody titers elicited were lower than those following intranasal immunization (a route already known to result in high-level systemic anti-TTFC immune responses) but the protective efficacy was the same order of magnitude. The serum antibody isotypes elicited were predominantly IgG1 and IgG2a. TTFC-specific fecal IgA responses could be detected following oral or intranasal immunization. Chemically killed lactococci administered via the intranasal route were also able to elicit serum antibody responses of similar levels and kinetics to those induced by live bacteria.

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          The mucosal immune system: from fundamental concepts to vaccine development

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            Potential of using lactic acid bacteria for therapy and immunomodulation in man.

            There is in 1993 no proven medical indication of lactic acid bacteria (LAB) for therapy or immunomodulation in man. However, within the bulk of publications, rigorous trials have now opened rational fields of research on beneficial effects of LAB. These include lactose digestion, cholesterol metabolism, diarrheal disorders, prophylaxis of intestinal or urogenital infections, immunomodulation or even oral vaccination. We try here to analyse these studies, considering LAB as pharmacological agents, and conclude that pursuit of research could be promising for ecological therapy of mucosal diseases, and for development of original and flexible vectors for targeting in the gastrointestinal tract.
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              Lactococcus lactis: high-level expression of tetanus toxin fragment C and protection against lethal challenge.

              To determine if the food-grade bacterium Lactococcus lactis holds promise as a vaccine antigen delivery vector we have investigated whether this bacterium can be made to produce high levels of a heterologous protein antigen. A regulated expression system has been developed which may be generally suitable for the expression of foreign antigens (and other proteins) in L. lactis. The system utilizes the fast-acting T7 RNA polymerase to transcribe target genes, and provides the first example of the successful use of this polymerase in a Gram-positive bacterium. When the performance of the expression system was characterized using tetanus toxin fragment C (TTFC) up to 22% of soluble cell protein was routinely obtained as TTFC. Mice immunized subcutaneously with L. lactis expressing TTFC were protected from lethal challenge with tetanus toxin. These results show for the first time that L. lactis is able to express substantial quantities of a heterologous protein antigen and that this organism can present this antigen to the immune system in an immunogenic form.
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