Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections

Abstract

Parasites of the genus Leishmania are unusual unicellular microorganisms in that they are characterized by the capability to subvert in their favor the immune response of mammalian phagocytes, including dendritic cells. Thus, in overt leishmaniasis, dendritic cells and macrophages are converted into a niche for Leishmania spp. in which the parasite, rather than being inactivated and disassembled, survives and replicates. In addition, Leishmania parasites hitchhike onto phagocytic cells, exploiting them as a mode of transport to lymphoid tissues where other phagocytic cells are potentially amenable to parasite colonization. This propensity of Leishmania spp. to target dendritic cells has led some researchers to consider the possibility that the non-pathogenic, reptile-associated Leishmania tarentolae could be exploited as a vaccine platform and vehicle for the production of antigens from different viruses and for the delivery of the antigens to dendritic cells and lymph nodes. In addition, as L. tarentolae can also be regarded as a surrogate of pathogenic Leishmania parasites, this parasite of reptiles could possibly be developed into a vaccine against human and canine leishmaniases, exploiting its immunological cross-reactivity with other Leishmania species, or, after its engineering, for the expression of antigens from pathogenic species. In this article we review published studies on the use of L. tarentolae as a vaccine platform and vehicle, mainly in the areas of leishmaniases and viral infections. In addition, a short summary of available knowledge on the biology of L. tarentolae is presented, together with information on the use of this microorganism as a micro-factory to produce antigens suitable for the serodiagnosis of viral and parasitic infections. Graphical Abstract

Live attenuated-nonpathogenic Leishmania and DNA structures as promising vaccine platforms against leishmaniasis: innovations can make waves

“…Leishmania tarentolae has also been investigated as vaccines against human pathogenic Leishmania species ( Bandi et al, 2023 ). After Breton et al showed that intra-peritoneal administration of live L. tarentolae in BALB/c mice induces a Th1 pathway with significant protection against L. donovani infectious challenge ( Breton et al, 2005 ), non-engineered live L. tarentolae promastigotes were assayed as candidate vaccines adjuvanted with CpG oligonucleotides ( Keshavarzian et al, 2020 ), or chitin microparticles against L. major ( Haghdoust et al, 2022 ; Noroozbeygi et al, 2023 ).…”

Use of Leishmania-Derived Extracellular Vesicles as a Vaccine Platform Against Emerging Viral Diseases

“…Of the various prokaryotic and eukaryotic systems explored, non-pathogenic Leishmania species have stood out as candidates with high potential 13 . Among these species, Leishmania tarentolae is one of the more attractive species as it can be cultured in inexpensive media at 26 °C and in large batches with a fairly short generation time (approximately 5-6 hours) [13][14][15] . Studies conducted in the late 2000s have shown that L. tarentolae can produce high yields of recombinant proteins.…”

Synthetic biology for combating leishmaniasis

“…Plasmids encoding L. infantum nucleosomal histones (H2A, H2B, H3, H4) were assessed in this context, demonstrating a strong Th1 response against CL ( Figure 2F ; Carrión, 2011 ; Moafi et al, 2019 ). Immuno-modulation of macrophages to polarize to M1 phenotype and to induce CD4+ T cells to polarize to Th1 phenotype was demonstrated by using L. tarentolae as a live vaccine against host as the parasite is reported to possess features that may be needed in an anti- Leishmania vaccine ( Bandi et al, 2023 ). PpSP15 and PsSP9 were proposed to be a protective vaccine for L. major and L. tropica infection, however, T2A (a peptide that self-cleaves derived from a virus) linked PpSP15 and PsSP9 demonstrated to induce Th1 protective immunity in L. tarentolae infection model ( Lajevardi et al, 2022 ).…”