Evaluation of immune responses and analysis of the effect of vaccination of the Leishmania major recombinant ribosomal proteins L3 or L5 in two different murine models of cutaneous leishmaniasis

Four new antigenic proteins located in Leishmania ribosomes have been characterized: S4, S6, L3 and L5. Recombinant versions of the four ribosomal proteins from Leishmania major were recognized by sera from human and canine patients suffering different clinical forms of leishmaniasis. The prophylactic properties of these proteins were first studied in the experimental model of cutaneous leishmaniasis caused by L. major inoculation into BALB/c mice. The administration of two of them, LmL3 or LmL5 combined with CpG-oligodeoxynucleotides (CpG-ODN) was able to protect BALB/c mice against L. major infection. Vaccinated mice showed smaller lesions and parasite burden compared to mice inoculated with vaccine diluent or vaccine adjuvant. Protection was correlated with an antigen-specific increased production of IFN-γ paralleled by a decrease of the antigen-specific IL-10 mediated response in protected mice relative to non-protected controls. Further, it was demonstrated that BALB/c mice vaccinated with recombinant LmL3 or LmL5 plus CpG-ODN were also protected against the development of cutaneous lesions following inoculation of L. braziliensis. Together, data presented here indicate that LmL3 or LmL5 ribosomal proteins combined with Th1 inducing adjuvants, may be relevant components of a vaccine against cutaneous leishmaniasis caused by distinct species. © 2013 Elsevier Ltd.Laboratorios LETI S.L.; Ministerio de Ciencia e Innovación FIS/PI080101 and FIS PI11/00095 and from the Instituto de Salud Carlos III within the Network of Tropical Diseases Research (RICET RD06/0021/0008); FAPEMIG (CBB-APQ-00496-11); CNPq (APQ-472090/2011-9); INCT NANO-BIOFAR; Fundación Ramón ArecesPeer Reviewe

Evaluation of immune responses and analysis of the effect of vaccination of the Leishmania major recombinant ribosomal proteins L3 or L5 in two different murine models of cutaneous leishmaniasis.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-19T19:22:11Z No. of bitstreams: 1 Ramirez L Evaluation....pdf: 942432 bytes, checksum: d979c74e2bb0c3869a3574c41612d9ee (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-19T19:22:21Z (GMT) No. of bitstreams: 1 Ramirez L Evaluation....pdf: 942432 bytes, checksum: d979c74e2bb0c3869a3574c41612d9ee (MD5)Made available in DSpace on 2014-09-19T19:36:54Z (GMT). No. of bitstreams: 1 Ramirez L Evaluation....pdf: 942432 bytes, checksum: d979c74e2bb0c3869a3574c41612d9ee (MD5) Previous issue date: 2013Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa. CSIC-UAM. Departamento de Biología Molecular. Madrid, SpainFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Minas Gerais. Faculdade de Medicina e Departamento de Patologia Clínica. COLTEC. Programa de Pós-Graduação em Ciências Saúde. I Infectologia e Medicina Tropical. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa. CSIC-UAM. Departamento de Biología Molecular. Madrid, SpainResearch & Development Department. Laboratorios LETI S.L.u. Madrid, SpainUniversidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa. CSIC-UAM. Departamento de Biología Molecular. Madrid, SpainFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa. CSIC-UAM. Departamento de Biología Molecular. Madrid, SpainFour new antigenic proteins located in Leishmania ribosomes have been characterized: S4, S6, L3 and L5. Recombinant versions of the four ribosomal proteins from Leishmania major were recognized by sera from human and canine patients suffering different clinical forms of leishmaniasis. The prophylactic properties of these proteins were first studied in the experimental model of cutaneous leishmaniasis caused by L. major inoculation into BALB/c mice. The administration of two of them, LmL3 or LmL5 combined with CpG-oligodeoxynucleotides (CpG-ODN) was able to protect BALB/c mice against L. major infection. Vaccinated mice showed smaller lesions and parasite burden compared to mice inoculated with vaccine diluent or vaccine adjuvant. Protection was correlated with an antigen-specific increased production of IFN-γ paralleled by a decrease of the antigen-specific IL-10 mediated response in protected mice relative to non-protected controls. Further, it was demonstrated that BALB/c mice vaccinated with recombinant LmL3 or LmL5 plus CpG-ODN were also protected against the development of cutaneous lesions following inoculation of L. braziliensis. Together, data presented here indicate that LmL3 or LmL5 ribosomal proteins combined with Th1 inducing adjuvants, may be relevant components of a vaccine against cutaneous leishmaniasis caused by distinct species