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

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.

Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution

“…Thus, suggesting that the changes observed in the proportion of T cell subsets are minimally affected by differences in cellularity. In addition, our results are in agreement with recent publications showing that CD8 + effector memory cells (Reyes-Sandoval et al, 2011; Rigato et al, 2011; Sánchez-Sampedro et al, 2012) and CD4 + effector memory cells (Sánchez-Sampedro et al, 2012) have a relevant role for long-term protective immunity against parasites in some vaccination approaches as these cells are able to mount a rapid response after encountering the antigen (Colpitts and Scott, 2010). Besides, despite the ethical difficulties of working with human spleen samples, we were able to determine that the number of T cells increased after exPv stimulation.…”

Cytotoxic T Cells Mediate Pathology and Metastasis in Cutaneous Leishmaniasis

“…Moreover, in several experimental vaccine models CD8+ T cells contribute to immunity [26], [27], [28], [29], [30], [31]. In contrast, we found that depletion of CD8+ T cells in L. braziliensis infected mice decreases inflammation.…”

Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

“…Jayakumar et al examined a prime-boost immunization with DNA-MVA encoding tryparedoxin peroxidase (TRYP) with TLR1/2 adjuvant and induced CD4 + /CD8 + /IFN-γ + T cell related protection in Balb/c mice against L. panamensis infection [42]. Same results were obtained by LACK DNA-MVA immunization reported by Sanchez-Sampedro [43]. Overally these results suggested that DNA vaccines as equivalents of low dose parasite or antigen administration are able to induce Th1 skewed immune responses against primary high dose parasite challenge.…”

“…Among possible vector combinations, Human Adenovirus [44], Modified Vaccinia Ankara [42,43] and Salmonella [45] have received significant attention. However antivector immunity is the main drawback linked with these vectors.…”