High quality long-term CD4+ and CD8+ effector memory populations stimulated by DNA-LACK/MVA-LACK regimen in Leishmania major BALB/c model of infection.
Heterologous vaccination based on priming with a plasmid DNA vector and boosting with an attenuated vaccinia virus MVA recombinant, with both vectors expressing the Leishmania infantum LACK antigen (DNA-LACK and MVA-LACK), has shown efficacy conferring protection in murine and canine models against cutaneus and visceral leishmaniasis, but the immune parameters of protection remain ill defined. Here we performed by flow cytometry an in depth analysis of the T cell populations induced in BALB/c mice during the vaccination protocol DNA-LACK/MVA-LACK, as well as after challenge with L. major parasites. In the adaptive response, there is a polyfunctional CD4(+) and CD8(+) T cell activation against LACK antigen. At the memory phase the heterologous vaccination induces high quality LACK-specific long-term CD4(+) and CD8(+) effector memory cells. After parasite challenge, there is a moderate boosting of LACK-specific CD4(+) and CD8(+) T cells. Anti-vector responses were largely CD8(+)-mediated. The immune parameters induced against LACK and triggered by the combined vaccination DNA/MVA protocol, like polyfunctionality of CD4(+) and CD8(+) T cells with an effector phenotype, could be relevant in protection against leishmaniasis.
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Lucas
L
Sánchez-Sampedro
Carmen Elena
CE
Gómez
Ernesto
E
Mejías-Pérez
Carlos Oscar S
CO
Sorzano
Mariano
M
Esteban
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004285:Dogs; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory / Q000187:drug effects*; D018320:Leishmania major / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D013997:Time Factors; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014616:Vaccinia virus
D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C093139:LACK antigen, Leishmania