Abstract
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.
Highlights
Leishmaniasis is one of the most neglected tropical diseases, prevalent in 88 countries presenting an estimated annual incidence of 2 million infections and about 12 million cases worldwide [1]
We have previously described a heterologous prime/boost vaccination approach based on DNA and vaccinia virus vectors that induced protection against L. major infection in immunized BALB/c mice and this effect was Th1-dependent [19]
To analyze in more detail the vaccine-specific immune responses triggered in BALB/c mice by a DNA-LACK/MVA-LACK immunization regimen, groups of mice were first primed intradermally (i.d.) with 100 mg of DNA-LACK or sham DNA (DNAw), and two weeks later the animals were boosted by intraperitoneal (i.p.) route with 26107 PFU/mouse of recombinant virus MVA-LACK or MVAwt
Summary
Leishmaniasis is one of the most neglected tropical diseases, prevalent in 88 countries presenting an estimated annual incidence of 2 million infections and about 12 million cases worldwide [1]. The goal in chemotherapy still remains a safe cheap oral drug and this objective appears to be distant for both major forms of the disease [2]. All these evidences point out the development of an effective vaccine as a major need against leishmaniasis. LACK, the leishmania homologue for receptors of activated C kinase, is a 36 kDa intracellular protein that is expressed in both stages of the parasite (amastigote and promastigote) [5], is highly conserved among Leishmania species [6] and is very immunogenic, being a preferential target for the early anti-parasite immune response. Some evidences pointed that this immune profile against LACK antigen can be altered, and this alteration is enough to induce resistance to infection [8]
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