The potential of live attenuated vaccines against Cutaneous Leishmaniasis

Zabala-Peñafiel, Anabel; Todd, D.; Daneshvar, Hamid; Burchmore, Richard

doi:10.1016/j.exppara.2020.107849

Cited by 25 publications

(25 citation statements)

References 78 publications

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“…The plasticity of the Leishmania genomes offers large ranges of genetic variants from which to select, both in the laboratory and in the wild, allowing them to overcome the loss or loss of function of single proteins. Thus, our data also highlight the risk of using genetically modified, live-attenuated Leishmania parasites [89][90][91] for vaccine purposes, since supposedly attenuating genetic modifications may be easily reversed or compensated through selection from pre-existing, beneficial gene amplification variants within Leishmania populations.…”

Section: Over Expression Of Casein Kinase 12 Rescues Temperature Tolmentioning

confidence: 85%

Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants

Kröber-Boncardo

Lorenzen

Brinker

et al. 2020

Sci Rep

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Leishmania donovani is a trypanosomatidic parasite and causes the lethal kala-azar fever, a neglected tropical disease. The Trypanosomatida are devoid of transcriptional gene regulation and rely on gene copy number variations and translational control for their adaption to changing conditions. To survive at mammalian tissue temperatures, L. donovani relies on the small heat shock protein HSP23, the loss of which renders the parasites stress sensitive and impairs their proliferation. Here, we analysed a spontaneous escape mutant with wild type-like in vitro growth. Further selection of this escape strains resulted in a complete reversion of the phenotype. Whole genome sequencing revealed a correlation between stress tolerance and the massive amplification of a six-gene cluster on chromosome 35, with further analysis showing over expression of the casein kinase 1.2 gene as responsible. In vitro phosphorylation experiments established both HSP23 and the related P23 co-chaperone as substrates and modulators of casein kinase 1.2, providing evidence for another crucial link between chaperones and signal transduction protein kinases in this early branching eukaryote.

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Section: Over Expression Of Casein Kinase 12 Rescues Temperature Tolmentioning

confidence: 85%

Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants

Kröber-Boncardo

Lorenzen

Brinker

et al. 2020

Sci Rep

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“…Since biosecurity concerns make problematic the use of infective forms, the use of attenuated cell lines offers the possibility of generate immunity without inducing the disease. This strategy, studied mainly for experimental models of VL [35] and CL caused by L. major and species for the Viannia subgenus like L. braziliensis [20] has not been extensively studied in the case of L. amazonensis.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, the use of attenuated strains for the generation of vaccines against visceral leishmaniasis (VL) [19] or CL [20] has proven to be an interesting alternative to the immunization of subunit-based vaccines. In this sense, there are very few references regarding the analysis of these vaccines in murine models of infection by L. amazonensis.…”

Section: Introductionmentioning

confidence: 99%

Inoculation of the Leishmania infantum HSP70-II Null Mutant Induces Long-Term Protection against L. amazonensis Infection in BALB/c Mice

et al. 2021

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Leishmania amazonensis parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to L. amazonensis challenge due to their inability to mount parasite-dependent IFN-γ-mediated responses. Here, we analyzed the capacity of a single administration of the LiΔHSP70-II genetically-modified attenuated L. infantum line in preventing cutaneous leishmaniasis in mice challenged with L. amazonensis virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to Old World Leishmania species. Vaccinated mice showed a reduction in the disease evolution due to L. amazonensis challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti-Leishmania IgG2a circulating antibodies accompanied to the induction of Leishmania-driven specific IFN-γ systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-ϒ production by CD4+ and CD8+ T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate LiΔHSP70-II as a candidate for the development of human vaccines.

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“…The vaccination strategies explored against leishmaniasis ranged from recombinant antigens, DNA vaccines, salivary gland proteins, killed parasites, and live attenuated parasites. The rich history of anti-leishmanial vaccines has been covered extensively in previous review articles on this theme (Kedzierski, 2011;Iborra et al, 2018;Kaye et al, 2020;Zabala-Peñafiel et al, 2020). For the purpose of brevity, a discussion on all the experimental vaccines is not being attempted in this article.…”

Section: Vaccination Strategies Against Leishmaniasismentioning

confidence: 99%

Revival of Leishmanization and Leishmanin

Pacheco-Fernández

Volpedo

Gannavaram

et al. 2021

Front. Cell. Infect. Microbiol.

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Leishmaniasis includes a spectrum of diseases ranging from debilitating cutaneous to fatal visceral infections. This disease is caused by the parasitic protozoa of the genus Leishmania that is transmitted by infected sandflies. Over 1 billion people are at risk of leishmaniasis with an annual incidence of over 2 million cases throughout tropical and subtropical regions in close to 100 countries. Leishmaniasis is the only human parasitic disease where vaccination has been successful through a procedure known as leishmanization that has been widely used for decades in the Middle East. Leishmanization involved intradermal inoculation of live Leishmania major parasites resulting in a skin lesion that following natural healing provided protective immunity to re-infection. Leishmanization is however no longer practiced due to safety and ethical concerns that the lesions at the site of inoculation that can last for months in some people. New genome editing technologies involving CRISPR has now made it possible to engineer safer attenuated strains of Leishmania, which induce protective immunity making way for a second generation leishmanization that can enter into human trials. A major consideration will be how the test the efficacy of a vaccine in the midst of the visceral leishmaniasis elimination program. One solution will be to use the leishmanin skin test (LST) that was also used for decades to determine exposure and immunity to Leishmania. The LST involves injection of antigen from Leishmania in the skin dermis resulting in a delayed type hypersensitivity (DTH) immune reaction associated with a Th1 immune response and protection against visceral leishmaniasis. Reintroduction of novel approaches for leishmanization and the leishmanin skin test can play a major role in eliminating leishmaniasis.

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The potential of live attenuated vaccines against Cutaneous Leishmaniasis

Cited by 25 publications

References 78 publications

Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants

Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants

Inoculation of the Leishmania infantum HSP70-II Null Mutant Induces Long-Term Protection against L. amazonensis Infection in BALB/c Mice

Revival of Leishmanization and Leishmanin

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