title: Characterization of the protective immune response to Yersinia pseudotuberculosis infection in mice vaccinated with an LcrV-secreting strain of Lactococcus lactis.
abstract: Pseudotuberculosis is an infection caused by the bacterial enteropathogen Yersinia pseudotuberculosis and is considered to be a significant problem in veterinary medicine. We previously found that intranasal administration of a recombinant Lactococcus lactis strain that secretes the low-calcium response V (LcrV) antigen from Y. pseudotuberculosis (Ll-LcrV) confers protection against a lethal Y. pseudotuberculosis infection. Here, we aimed at characterizing the immunological basis of this LcrV-elicited protective response and at determining the duration of vaccine-induced immunity.
  
  
  
  Splenocytes from BALB/c mice intranasally immunized with Ll-LcrV or Ll as control were immunostained then analyzed by flow cytometry. Protection against a lethal intravenous injection of Y. pseudotuberculosis was also determined (i) in immunized BALB/c mice depleted or not of CD4+, CD8+or CD25+cells and (ii) in naïve BALB/c mice receiving serum from immunized mice by counting the number of bacteria in liver and spleen. Lastly, survival rate of immunized BALB/c mice following a lethal intravenous injection of Y. pseudotuberculosis was followed up to 9-months.
  
  
  
  We found that T and B lymphocytes but not non-conventional lymphoid cells were affected by Ll-LcrV immunization. We also observed that depletion of CD4+and CD25+but not CD8+cells in immunized mice eradicated protection against a lethal systemic Y. pseudotuberculosis infection, suggesting that activated CD4+T lymphocytes are required for vaccine-induced protection. Adoptive transfer of LcrV-specific antibodies from Ll-LcrV-immunized animals significantly reduced the bacterial counts in the liver compared to non-vaccinated mice. Lastly, the protective immunity conferred by Ll-LcrV decreased slightly over time; nevertheless almost 60% of the mice survived a lethal bacterial challenge at 9months post-vaccination.
  
  
  
  Mucosal vaccination of mice with Ll-LcrV induced cell- and antibody-mediated protective immunity against Y. pseudotuberculosis infection in the mouse and the protection is long-lasting.
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Titecat
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Poiret
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cayet
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Boutillier
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Simonet
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lemaître
authors.affiliation: Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France. Electronic address: florent.sebbane@inserm.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Sebbane
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007110:Immunity, Active / Q000276:immunology*; D007275:Injections, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000276:immunology*; D015012:Yersinia pseudotuberculosis Infections / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D015704:CD4 Antigens; D016827:CD8 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D014614:Vaccines, Synthetic
keywords: Lactococcus lactis; LcrV; Vaccination; Yersinia