Donata Medaglini

Publications (24)86.77 Total impact

• Article: Immunogenicity of the B Monomer of Escherichia coli Heat-Labile Toxin Expressed on the Surface of Streptococcus gordonii

  Susanna Ricci, Donata Medaglini, Catherine M. Rush, Alessandro Marcello, Samuele Peppoloni, Riccardo Manganelli, Giorgio Palú, Gianni Pozzi
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  ABSTRACT: The B monomer of the Escherichia coli heat-labile toxin (LTB) was expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant bacteria expressing LTB were used to immunize BALB/c mice subcutaneously and intragastrically. The LTB monomer expressed on the streptococcal surface proved to be highly immunogenic, as LTB-specific immunoglobulin G (IgG) serum titers of 140,000 were induced after systemic immunization. Most significantly, these antibodies were capable of neutralizing the enterotoxin in a cell neutralization assay. Following mucosal delivery, antigen-specific IgA antibodies were found in feces and antigen-specific IgG antibodies were found in sera. Analysis of serum IgG subclasses showed a clear predominance of IgG1 when recombinant bacteria were inoculated subcutaneously, while a prevalence of IgG2a was observed upon intragastric delivery, suggesting, in this case, the recruitment of a Th1 type of immune response.
  Infection and Immunity 03/2000; · 4.16 Impact Factor
• Source

  Available from: Marco Oggioni

  Article: Recombinant Gram-positive bacteria as vehicles of vaccine antigens

  Donata Medaglini, Susanna Ricci, Tiziana Maggi, Catherine M. Rush, Riccardo Manganelli, Marco R. Oggioni, Gianni Pozzi
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  ABSTRACT: AbstractGram-positive bacteria which are being developed as vaccine delivery systems include Lactococcus lactis, Lactobacillus spp., Streptococcus gordonii, nonpathogenic species of Staphylococcus, and Listeria. The use of these microorganisms relies on the fact that they are safe vehicles that can efficiently target vaccine antigens to the immune system. Two main approaches have been followed, according to the capacity of the bacterial vehicle to colonise the mucosal surfaces. Colonisers such as S. gordonii and some Lactobacilli can stimulate immune system by being transiently implanted among the normal flora of the host, while other lactobacilli, lactococci and staphylococci persist very shortly in the host and therefore their ability to generate an immune response must rely on high-level expression of the recombinant antigen. The immunogenicity of recombinant antigens by mucosal delivery has been demonstrated using colonising (S. gordonii) and noncolonising (Lc. lactis) bacterial vehicles. There is also great potential in the cellular responses induced by recombinant Listeria.
  Biotechnology Annual Review.
• Article: Commensal bacteria as vectors for mucosal vaccines against sexually transmitted diseases: vaginal colonization with recombinant streptococci induces local and systemic antibodies in mice

  Donata Medaglini, Catherine M. Rush, Piersante Sestini, Gianni Pozzi
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  ABSTRACT: There is a need to develop vaccines to control the spread of sexually transmitted diseases (STDs). Novel immunization strategies that elicit a mucosal immune response in the genital tract, may show improved protection by preventing or at least limiting entry of the pathogenic micro-organism. However, it has proven difficult to obtain a local immune response in the vaginal mucosa. Our approach is based on the use of recombinant bacteria capable of colonizing mucosal surfaces as live vaccine vectors. The human commensal Streptococcus gordonii, engineered to express the E7 protein of human papillomavirus type 16, was used for intravaginal immunization of mice. A single inoculum of recombinant bacteria was sufficient to establish colonization of the murine vagina and therefore induce papillomavirus-specific vaginal IgA and serum IgG. Evidence that mucosal colonization with recombinant commensal bacteria can induce a local immune response in the female genital tract represents a significant step toward the development of new vaccines against STDs.
  Vaccine · 3.77 Impact Factor
• Article: Immunoglobulin-binding domains of peptostreptococcal protein L enhance vaginal colonization of mice by Streptococcus gordonii

  Susanna Ricci, Donata Medaglini, Harold Marcotte, Arne Olsén, Gianni Pozzi, Lars Björck
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  ABSTRACT: Protein L, an immunoglobulin-binding protein of some strains of the anaerobic bacteriumPeptoÍstreptococcus magnus , has been hypothesized to be a virulence determinant in bacterial vaginosis. In order to investigate the role of protein L in peptostreptococcal virulence, the Ig-binding domains of protein L were expressed at the surface of the human oral commensal Streptococcus gordonii. Recombinant streptococci were used in vaginal colonization experiments, and protein L-expressing S. gordonii demonstrated enhanced ability to colonize the vaginal mucosa. Compared to the control strain, they also persisted for a longer period in the murine vagina.
  Microbial Pathogenesis.