Downregulation of IRF7-mediated type-I interferon response by LmCen parasites is necessary for protective immunity.

Leishmaniasis is a tropical disease caused by Leishmania parasites and currently has no licensed vaccines. We developed a dermotropic Leishmania major centrin gene-deleted strain (LmCen) as a live attenuated vaccine. Recent studies have shown that type I interferons (IFNs) play important roles in immunity to parasitic and viral pathogens.

Manufacturing and preclinical toxicity of GLP grade gene deleted attenuated Leishmania donovani parasite vaccine.

Centrin1 gene deleted Leishmania donovani parasite (LdCen1) was developed and extensively tested experimentally as an intracellular stage-specific attenuated and immunoprotective live parasite vaccine candidate ex vivo using human PBMCs and in vivo in animals. Here we report manufacturing and pre-clinical evaluation of current Good-Laboratory Practice (cGLP) grade LdCen1 parasites, as a prerequisite before proceeding with clinical trials. We screened three batches of LdCen1 parasites manufactured in bioreactors under cGLP conditions, for their consistency in genetic stability, attenuation, and safety.

Immunization with -Deficient Does Not Protect against Homologous Challenge.

Immunization with various species lacking induces robust immunity against a homologous and heterologous virulent challenge, making mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and spp. lacking centrin are unable to replicate and are non-pathogenic.

The Preclinical Validation of 405 nm Light Parasiticidal Efficacy on in Ex Vivo Platelets in a Rag2 Mouse Model.

Violet-blue light of 405 nm in the visible spectrum at a dose of 270 J/cm alone has been shown to be an effective microbicidal tool for inactivating several bacteria, HIV-1, and in ex vivo plasma and platelets. Unlike chemical- and ultraviolet (UV)-based pathogen inactivation methods for plasma and platelet safety, 405 nm light is shown to be less toxic to host cells at light doses that are microbicidal. In this report, we evaluated the parasiticidal activity of a 405 nm light treatment on platelets spiked with the parasite.

promotes pain-reducing metabolomic reprogramming in cutaneous lesions.

Cutaneous leishmaniasis (CL) is characterized by extensive skin lesions, which are usually painless despite being associated with extensive inflammation. The molecular mechanisms responsible for this analgesia have not been identified. Through untargeted metabolomics, we found enriched anti-nociceptive metabolic pathways in -infected mice.