Grupos de Investigación
Sede San Martín

Laboratorio de Inmunología, enfermedades infecciosas y desarollo de vacunas.

Integrantes

Director:

Dra. Juliana Cassataro

Investigadora Independiente CONICET

Miembros actuales
Dra. Karina Pasquevich (Investigadora Asistente CONICET)

Dra. Lorena Coria, becaria Posdoctoral Bunge y Born

Lic. Marianela Carabajal, becaria de posgrado tipo II CONICET.

Bioq. Laura Darriba, becaria doctoral CONICET.

Lic. Franco Martinez, becario doctoral ANPCyT.

Laura Bruno, técnica auxiliar.

Líneas de investigación

Utilidad de dos proteinas de Brucella spp. como adyuvantes en formulaciones vacunales contra enfermedades infecciosas y alergias.

Búsqueda de nuevos adyuvantes para vacunas administradas por vía oral.

Estudio de un inhibidor de proteasas y su rol en la transmisión oral, supervivencia intracelular y escape de Brucella abortus frente a la respuesta inmune.

Publicaciones

En revistas internacionales con referato:

  1. Coria LM, Ibañez AE, Tkach M, Sabbione F, Bruno L, Carabajal MV, Berguer PM, Barrionuevo P, Schillaci R, Trevani AS, Giambartolomei GH, Pasquevich KA, Cassataro J.A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses. J Immunol. 2016 May 15;196(10):4014-29.
  2. Lorena M. Coria, Andrés E. Ibañez, Karina A. Pasquevich, Paula L. González Cobiello, Fernanda M. Frank, Guillermo H. Giambartolomei, Juliana Cassataro. Brucella abortus Omp19 recombinant protein subcutaneously co-delivered with an antigen enhances antigen-specific T helper 1 memory responses and induces protection against parasite challenge. Vaccine. 2016 Jan 20;34(4):430-7.
  3. Ibañez AE, Coria LM, Carabajal MV, Delpino MV, Risso GS, Cobiello PG, Rinaldi J, Barrionuevo P, Bruno L, Frank F, Klinke S, Goldbaum FA, Briones G, Giambartolomei GH, Pasquevich KA, Cassataro J.A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses. J Control Release. 2015 Oct 9;220(Pt A):18-28.
  4. Ibañez AE, Coria LM, Carabajal MV, Delpino MV, Risso GS, Cobiello PG, Rinaldi J, Barrionuevo P, Bruno L, Frank F, Klinke S, Goldbaum FA, Briones G, Giambartolomei GH, Pasquevich KA, Cassataro J.A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses. J Control Release. 2015 Oct 9;220(Pt A):18-28.
  5. Smaldini PL, Ibañez AE, Fossati CA, Cassataro J, Docena GH. Oral delivery of Brucella spp. recombinant protein U-Omp16 abrogates the IgE-mediated milk allergy.Hum Vaccin Immunother. 2014;10(7):2015-23.
  6. Clausse M, Díaz AG, Ibañez AE, Cassataro J, Giambartolomei GH, Estein SM. Evaluation of the efficacy of Outer Membrane Protein 31 vaccine formulations for protection against Brucella canis in BALB/c mice. Clin Vaccine Immunol. 2014 Oct. 00527-14.
  7. Roset MS, Ibañez AE, de Souza Filho JA, Spera JM, Minatel L, Oliveira SC, Giambartolomei GH, Cassataro J, Briones G. Brucella cyclic β-1,2-glucan plays a critical role in the induction of splenomegaly in mice. PLoS One. 2014. 1;9(7):e101279.
  8. Clausse M, Díaz AG, Ghersi G, Zylberman V, Cassataro J, Giambartolomei GG, Goldbaum FA, Estein SM. The vaccine candidate BLSOmp31 protects mice against Brucella canis infection. Vaccine. 2013. 31(51):6129-35..
  9. Ibañez A. E, Smaldini P, Coria L. M, Delpino M. V, Pacifico L.G.G, Oliveira S. C, Risso G. S, Pasquevich K.A, Fossati C. A, Giambartolomei G. H, Docena G. H, Cassataro J. Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as nasal adjuvant induces a Th1 immune response and modulates the Th2 allergic response to Cow´s Milk Proteins. Plos One. 2013. 8(7):e69438.
  10. de Almeida LA, Macedo GC, Marinho FA, Gomes MT, Corsetti PP, Silva AM, Cassataro J, Giambartolomei GH, Oliveira SC. Toll-Like Receptor 6 Plays an Important Role in Host Innate Resistance to Brucella abortus Infection in Mice. Infect Immun. 2013.81(5):1654-62.
  11. Miraglia MC, Scian R, Samartino CG, Barrionuevo P, Rodriguez AM, Ibañez AE, Coria LM, Velásquez LN, Baldi PC, Cassataro J, Delpino MV, Giambartolomei GH. Brucella abortus induces TNF-α-dependent astroglial MMP-9 secretion through mitogen-activated protein kinases.J Neuroinflammation. 2013. 10:47.
  12. Barrionuevo P, Delpino MV, Pozner RG, Velásquez LN, Cassataro J, Giambartolomei GH. Brucella abortus induces intracellular retention of MHC-I molecules in human macrophages down-modulating cytotoxic CD8(+) T cell responses. Cell Microbiol. 2013.
  13. Tkach Mercedes, Coria L, Rosemblit C, Proietti CJ, Rivas MA, Dıaz Flaquem MC, Beguelin W, Frahm I, Charreau EH, Cassataro J, Elizalde PV and Schillaci R. Targeting Stat3 Induces Senescence in Tumor Cells and Elicits Prophylactic and Therapeutic Immune Responses against Breast Cancer Growth Mediated by NK Cells and CD4+ T Cells. The Journal of Immunology. 2012. 189(3):1162-72.
  14. Velásquez LN, Delpino MV, Ibañez AE, Coria LM, Miraglia MC, Scian R, Cassataro J, Giambartolomei GH, Barrionuevo P. Brucella abortus induces apoptosis of human T lymphocytes. Microbes and Infection. 2012. 14(7-8):639-50.
  15. Oliveira SC, Giambartolomei GH, Cassataro J. Confronting the barriers to develop novel vaccines against brucellosis. Expert Review of Vaccines. 2011. (9):1291-305.
  16. Pasquevich KA, Ibañez AE, Coria LM, García Samartino C, Estein SM, Zwerdling A, Barrionuevo P, Souza de Oliveira F, Seither C, Warzecha H, Costa Oliveira S, Giambartolomei GH, Cassataro J. An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice. Plos One. 2011. 6(1):e16203.
  17. Barrionuevo P., Delpino M. V., Velásquez L. N., García Samartino C., Coria M. L., Ibañez A. E., Rodríguez M. E., Cassataro J., Giambartolomei G. H. Brucella abortus inhibits IFN-γ-induced FcγRI expression and FcγRI-restricted phagocytosis via Toll-Like Receptor 2 on human monocytes/macrophages. Microbes and Infection. 2011. 13(3):239-50.
  18. Costa Oliveira S, Costa Macedo G, Augusto de Almeida L, Souza de Oliveira F, Onãte A, Cassataro J, Giambartolomei GH. Recent advances in understanding immunity against brucellosis: application for vaccine development. Review. The Open Veterinary Science Journal. 4:101-107.
  19. Pasquevich KA, García Samartino C, Coria LM, Estein SM, Zwerdling A, Ibañez AE, Barrionuevo P, Souza de Oliveira F, Barbosa Carvalho N, Borkowski J, Costa Oliveira S, Warzecha H, Giambartolomei GH, Cassataro J. The protein moiety of Brucella abortus outer membrane protein Omp16 is a new bacterial pathogen associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. The Journal of Immunology. 2010. 184(9):5200-12.
  20. García Samartino C, Delpino MV, Pott Godoy C, Di Genaro MS, Pasquevich KA, Zwerdling A, Barrionuevo P, Mathieu P, Cassataro J, Pitossi F, Giambartolomei GH. Brucella abortus Induces The Secretion of Pro-inflammatory Mediators From Glial Cells Leading to Astrocyte Apoptosis. The American Journal of Pathology. 2010. 176(3):1323-38.
  21. Estein SM, Fiorentino MA, Paolicchi FA, Clausse M, Manazza J, Cassataro J, Giambartolomei GH, Coria LM, Zylberman V, Fossati CA, Kjeken R, Goldbaum FA. The polymeric antigen BLSOmp31 confers protection against Brucella ovis infection in rams. Vaccine. 2009. 27(48):6704-11.
  22. Zwerdling A, Delpino MV, Pasquevich KA, Barrionuevo P, Cassataro J, Samartino CG, Giambartolomei GH. Brucella abortus activates human neutrophils. Microbes and Infection. 2009. 11(6-7): 689-97.
  23. Pasquevich KA, Estein SM, García Samartino C, Zwerdling A, Coria LM, Barrionuevo P, Fossati CA, Giambartolomei GH, Cassataro J. Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection. Infection and Immunity. 2009. 77(1):436-45.
  24. Zwerdling, A Delpino MV, Barrionuevo P, Cassataro J, Pasquevich K A, García Samartino C, Fossati CA y Giambartolomei GH. Brucella lipoproteins mimic dendritic cell maturation induced by Brucella abortus. Microbes and Infection. 2008. 10(12-13):1346-54.
  25. Barrionuevo P, Cassataro J, Delpino MV, Zwerdling A, Pasquevich KA, García Samartino C, Wallach JC, Fossati CA, Giambartolomei GH. Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin-6 secretion via Toll-like receptor 2. Infection and Immunity. 2008. 76(1):250-62.
  26. Delpino MV, Estein SM, Fossati CA, Baldi PC, Cassataro J. Vaccination with Brucella recombinant DnaK and SurA proteins induces protection against Brucella abortus infection in BALB/c mice. Vaccine. 2007. 25(37-38):6721-9.
  27. Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Zwerdling A, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA. A DNA vaccine coding for the chimera BLSOmp31 induced a better degree of protection against B. ovis and a similar degree of protection against B. melitensis than Rev.1 vaccination. Vaccine. 2007. 25(32):5958-67.
  28. Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Velikovsky CA, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA. A recombinant subunit vaccine based on the insertion of 27 aminoacids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev-1 vaccination. Vaccine. 2007.25(22):4437-46.
  29. Cassataro J, Velikovsky CA, Bruno L, Estein SM, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH. Improved Immunogenicity of a Brucella DNA vaccine encoding Outer Membrane Protein 31 (Omp31) by Recombinant Omp31 Boosting. Clinical and Vaccine Immunology. 2007. 14(7):869-74.
  30. Delpino MV, Marchesini MI, Estein SM, Comerci DJ, Cassataro J, Fossati CA, Baldi PC. A bile salt hydrolase of Brucella abortus contributes to the establishment of a successful infection through the oral route in mice. Infection and Immunity. 2007. 75(1):299-305.
  31. Schillaci R, Salatino M, Cassataro J, Proietti CJ, Giambartolomei GH, Rivas MA, Carnevale RP, Charreau EH, Elizalde PV. Immunization with Murine Breast Cancer Cells Treated with Antisense Oligodeoxynucleotides to Type I Insulin-Like Growth Factor Receptor Induced an Antitumoral Effect Mediated by a CD8+ Response Involving Fas/Fas Ligand Cytotoxic Pathway. The Journal of Immunology. 2006. 176(6):3426-37.
  32. Delpino MV, Cassataro J, Fossati CA, Goldbaum FA, Baldi PC. Brucella outer membrane protein Omp31 is a haemin-binding protein. Microbes and Infection. 2006. (5):1203-8.
  33. Cassataro J, Estein S, Pasquevich K, Velikovsky CA, De la Barrera S, Bowden RA, Fossati CA, Giambartolomei GH. Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27 amino acid synthetic septide elicits a CD4+ T helper 1 response that protects against B. melitensis infection. Infection and Immunity. 2005.73(12):8079-88.
  34. Cassataro J, Velikovsky CA, De la Barrera S, Estein S, Bruno L, Bowden RA, Pasquevich K, Fossati CA, Giambartolomei GH. A DNA Vaccine Coding for the Brucella Outer Membrane Protein 31 Confers Protection against B. melitensis and B. ovis Infection by Eliciting a Specific Cytotoxic Response. Infection and Immunity. 2005. 73(10):6537-46.
  35. Giambartolomei GH, Zwerdling A, Cassataro J, Bruno L, Fossati CA, Phillip M. Lipoproteins, not lipopolysacharide, are the key mediators of the pro-inflammatory response elicited by Heat-Killed Brucella abortus. Journal of Immunology. 2004. 173(7):4635-42.
  36. S M. Estein, P Cheves, M A. Fiorentino, J Cassataro, F A. Paolicchib, R A. Bowden. Immunogenicity of recombinant Omp31 from Brucella melitensis in rams and serum bactericidal activity against B. ovis. Veterinary Microbiology. 2004. 102(3-4):203-13.
  37. Cassataro J, Pasquevich K, Bruno L, Wallach JC, Fossati CA, Baldi PC. Antibody reactivity to Omp31 from Brucella melitensis in human and animal infections by smooth and rough Brucellae.Clin Diagn Lab Immunol. 2004. (1):111-4.
  38. Velikovsky CA, Goldbaum FA, Cassataro J, Estein S, Bowden RA, Bruno L, Fossati CA, Giambartolomei GH. Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used. Infect Immun. 2003.71(10):5750-5.
  39. Estein SM, Cassataro J, Vizcaino N, Zygmunt MS, Cloeckaert A, Bowden RA. The recombinant Omp31 from Brucella melitensis alone or associated with rough lipopolysaccharide induces protection against Brucella ovis infection in BALB/c mice. Microbes Infect. 2003. (2):85-93.
  40. Delpino MV, Cassataro J, Fossati CA, Baldi PC. Antibodies to the CP24 protein of Brucella melitensis lack diagnostic usefulness in ovine brucellosis. Vet Microbiol. 2003. 93(2):101-7.
  41. Velikovsky CA, Cassataro J, Giambartolomei GH, Goldbaum FA, Estein S, Bowden RA, Bruno L, Fossati CA, Spitz M. A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice.Infect Immun. 2002. 70(5):2507-11.
  42. Cassataro J, Delpino MV, Velikovsky CA, Bruno L, Fossati CA, Baldi PC. Diagnostic usefulness of antibodies against ribosome recycling factor from Brucella melitensis in human or canine brucellosis.Clin Diagn Lab Immunol. 2002. 9(2):366-9.
  43. Cassataro J, Velikovsky CA, Giambartolomei GH, Estein S, Bruno L, Cloeckaert A, Bowden RA, Spitz M, Fossati CA. Immunogenicity of the Brucella melitensis recombinant ribosome recycling factor-homologous protein and its cDNA. Vaccine. 2002. 20(11-12):1660-9.
  44. Piroli GG, Cassataro J, Pietranera L, Grillo CA, Ferrini M, Lux-Lantos V, De Nicola AF. Progestin regulation of galanin and prolactin gene expression in oestrogen-induced pituitary tumours.J Neuroendocrinol. 2001.13(3):302-9.
  45. Velikovsky CA, Cassataro J, Sanchez M, Fossati CA, Fainboim L, Spitz M. Single-shot plasmid DNA intrasplenic immunization for the production of monoclonal antibodies. Persistent expression of DNA. J Immunol Methods. 2000. 244(1-2):1-7.

En revistas nacionales con referato:

  1. Moisés Spitz, Carlos A Velikovsky, Juliana Cassataro, Guillermo H. Giambartolomei. El rol de las secuencias CpG en las vacunas de ADN. Los receptores Toll y las vacunas génicas. Review. Medicina. 2002;62(1):99-102.

Capitulos en libros

  1. Pablo C. Baldi, Juliana Cassataro, Diego J. Comerci, Silvia Estein, Carlos A. Fossati, Guillermo H. Giambartolomei, Fernando A. Goldbaum, Jorge C. Wallach. BRUCELLA. En: Microbiología veterinaria. Capítulo 39, páginas 281-293. Editor Jefe: Nestor Oscar Stanchi. Editorial Intermédica, Buenos Aires (2007) ISBN N° 978-950-555-321-1
  2. Goldbaum FA, Baldi PC, Velikovsky CA, Giambartolomei GH, Wallach JC, Cassataro J, Spitz M, Fossati CA. Caracterización molecular de las proteínas bacterianas y su aplicación en el diagnóstico y la inmunoprofilaxis de la brucelosis. En: "Inmunopatología molecular: nuevas fronteras de la medicina. Un nexo entre la investigación biomédica y la práctica clínica". Editorial Panamericana. (G.A. Rabinovich, editor). Argentina, 1ra. edición año 2004. Capítulo 22, páginas 229-238.

Patentes:

  1. "Adjuvant for vaccines, vaccines that comprise it and uses". Acta de presentación: PCT/ES2010/070667. Aprobada en Argentina, Unión Europa y China. Presentada y esperando resolución en USA, Brasil, Canadá, India y Mexico. Inventores: Coria, Pasquevich, Ibañez, Giambartolomei, Delpino, Cassataro.
  2. "Proteínas quiméricas aisladas de Lumazina sintetasa modificada para la presentación múltiple de moléculas y sus aplicaciones”. P040101923 (Instituto Nacional de Propiedad Intelectual) Argentina. Inventores: Fernando Alberto Goldbaum, Diego Andrés Laplagne, Vanesa Zylberman, Patricio Craig, Paula Mercedes Berguer, Natalia Ainciart, Carlos Alberto Fossati, Carlos Alejandro Velikovsky, Juliana Cassataro, Guillermo Giambartolomei. Patente Nº US2005019289. “Isolated chimeric proteins of modified lumazine synthase”. Oficina de Patentes europea. Institución solicitante: Goldgene LLC.