2017
DOI: 10.1371/journal.pntd.0005527
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Abstract: BackgroundVisceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. H… Show more

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Cited by 114 publications
(119 citation statements)
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“…in animal models, but their safety and efficacy in humans remain controversial [162,[165][166][167]. However, some candidates were shown to be immunogenic in clinical trials, including an adenoviral-based platform (ChAd63-KH) encoding a polyprotein (a combination of kinetoplastid membrane protein-11 [KMP-11] and hydrophilic acylated surface protein B [HASPB] genes from L. donovani), which induced parasite-specific CD8+ T cell responses when tested in Phase I trials, suggesting its potential use as prophylactic and therapeutic vaccine for VL or PKDL [168]. Contrasting with DNA vaccines, mRNAs associated or not with viral vectors have the advantage of accumulating in the cytoplasm and being degraded once proteins are translated, thus minimizing the risks of integration of foreign genetic material into the host genome.…”
Section: Vaccines For Leishmaniasismentioning
confidence: 99%
“…in animal models, but their safety and efficacy in humans remain controversial [162,[165][166][167]. However, some candidates were shown to be immunogenic in clinical trials, including an adenoviral-based platform (ChAd63-KH) encoding a polyprotein (a combination of kinetoplastid membrane protein-11 [KMP-11] and hydrophilic acylated surface protein B [HASPB] genes from L. donovani), which induced parasite-specific CD8+ T cell responses when tested in Phase I trials, suggesting its potential use as prophylactic and therapeutic vaccine for VL or PKDL [168]. Contrasting with DNA vaccines, mRNAs associated or not with viral vectors have the advantage of accumulating in the cytoplasm and being degraded once proteins are translated, thus minimizing the risks of integration of foreign genetic material into the host genome.…”
Section: Vaccines For Leishmaniasismentioning
confidence: 99%
“…This vector was assessed with and without an MVA booster dose, and was found to elicit strong antibody and T‐cell responses, which could be increased in magnitude and durability by an MVA boost. Another chimpanzee adenoviral vector, ChAd63, has also been evaluated in several clinical trials (malaria, leishmaniasis) with results showing excellent safety and immunogenicity, even in infants and children.…”
Section: Enhanced Adenoviral Vectorsmentioning
confidence: 99%
“…Earlier, LEISH-F1 in combination with MPL-SE adjuvant also showed strong antigen-specific immune response in healthy people living in a L. donovani endemic area [6]. More recently, a third-generation DNA vaccine approach that employed simian adenovirus expressing a novel synthetic gene encoding Leishmania antigens, hence termed as ChAd63-KH, has shown potentiality to be a safe and immunogenic therapeutic vaccine for human VL and post kala-azar dermal leishmaniasis (PKDL) in a phase I trial [7]. Despite the ongoing progresses in vaccine development, the priority objective has not yet been achieved, i.e.…”
Section: Introductionmentioning
confidence: 99%