Development of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection

Duthie, Malcolm S.; Peña, María; Khandhar, Amit P.; Picone, Alessandro; MacMillen, Zachary; Truman, Richard W.; Adams, Linda B.; Reed, Steven G.

doi:10.1007/s00253-020-10505-2

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Notable genetic differences between the species included the presence in M. lepromatosis of the coproporphyrinogen III oxidase (hemN) gene, which is present in M. tuberculosis but absent from M. leprae, and relatively large variation in ESX-1 secreted protein genes associated with mycobacterial virulence (Ates et al, 2016). One of these, espA with 78% protein identity (Singh et al, 2015), codes for part of the LID-1 fusion protein developed as a serological test of HD (Duthie et al, 2020), raising the possibility that this test might be less sensitive for M. lepromatosis infection. Given concerns that the 98% identity of 16S rDNA sequences in the two species could yield unreliable PCR results when using primers for this region, the recent development and validation of a unique repetitive element PCR assay for M. lepromatosis (RLPM, equivalent to RLEP M. leprae) provide a reliable diagnostic method with which to investigate further this new species as a causative agent of HD (Sharma et al, 2020).…”

Section: Genomics and Phylogeneticsmentioning

confidence: 99%

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Deps

Collin

2021

Front. Microbiol.

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Mycobacterium lepromatosis was identified as a new species and second causal agent of Hansen’s disease (HD, or leprosy) in 2008, 150years after the disease was first attributed to Mycobacterium leprae. M. lepromatosis has been implicated in a small number of HD cases, and clinical aspects of HD caused by M. lepromatosis are poorly characterized. HD is a recognized zoonosis through transmission of M. leprae from armadillos, but the role of M. lepromatosis as a zoonotic agent of HD is unknown. M. lepromatosis was initially associated with diffuse lepromatous leprosy, but subsequent case reports and surveys have linked it to other forms of HD. HD caused by M. lepromatosis has been reported from three endemic countries: Brazil, Myanmar, and Philippines, and three non-endemic countries: Mexico, Malaysia, and United States. Contact with armadillos in Mexico was mentioned in 2/21 M. lepromatosis HD case reports since 2008. M. lepromatosis in animals has been investigated only in non-endemic countries, in squirrels and chipmunks in Europe, white-throated woodrats in Mexico, and armadillos in the United States. To date, there have only been a small number of positive findings in Eurasian red squirrels in Britain and Ireland. A single study of environmental samples found no M. lepromatosis in soil from a Scottish red squirrel habitat. Future studies must focus on endemic countries to determine the true proportion of HD cases caused by M. lepromatosis, and whether viable M. lepromatosis occurs in non-human sources.

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Section: Genomics and Phylogeneticsmentioning

confidence: 99%

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Deps

Collin

2021

Front. Microbiol.

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“…They found that armadillos expressed a strong IFN‐γ response to these same antigens. Armadillos have also been recently used to test new skin test reagents 121 . Collectively, these studies support the utility of these defined animal models of M. leprae infection for examining antigens currently under consideration for improved T cell–based diagnostic assays for leprosy in humans.…”

Section: Contributions Of the Mouse Modelmentioning

confidence: 67%

Susceptibility and resistance in leprosy: Studies in the mouse model

Adams

2021

Immunological Reviews

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“…Nonetheless, several multi-epitope constructs are already described as being effective, for example, LID-1, a fusion construct of ML0405 and ML2331 that can diagnose MB leprosy 6 to 8 months prior to the onset of clinical symptoms [14]. LepReact, a delayed-type hypersensitivity skin test, made from LID-1, was able to detect antigen-specific immune responses from M. leprae in guinea pigs and armadillos [72]. As to other diseases, Chagas disease detection can be improved using TcF43 and TcF26, proteins derived from the fusion of selected T. cruzi TR proteins [28]; Yin et al validated a high-accuracy ELISA assay using a recombinant protein for diagnosis of human brucellosis [27]; Ebrahimi [32].…”

Section: Discussionmentioning

confidence: 99%

In silico designing of a recombinant multi-epitope antigen for leprosy diagnosis

Lemes

Rodrigues

Jaiswal

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Most of the affected population lives in low-income countries and may take up to 10 years to show any clinical signs, which is how physicians diagnose it. However, due to progressive cell damage, early diagnosis is very important. The best way to confirm leprosy is through bacilloscopic, which only confirms the diagnosis and has low accuracy or PCR, that requires specialized operators and is expensive. Since the bacteria are fastidious and do not grow in any culture media, therefore, diagnosing leprosy in the lab is still a challenge. In this concern, a recombinant multi-epitope protein can be a beneficial strategy in the management of the diagnosis, as diverse immunogenic epitopes are precisely selected to detect specific antibodies. Therefore, the purposes of the present study were to select immunogenic epitopes from different relevant proteins, with immunogenic properties, and then to construct a recombinant multi-epitope protein that accuses the presence of the antibodies in the early stages of the disease, making it more than appropriate to be applied as a diagnostic tool. Results We selected 22 common proteins from both species and, using bioinformatics tools, predicted B and T cell epitopes. After multiple filtering and analyzing, we ended up with 29 epitopes {MHC-I (total 18) and MHC-II (total 11)} from 10 proteins, which were then merged into one construct. Its secondary and tertiary structures were also predicted and refined to comprise the amino acid residues in the best conformation possible. The multi-epitope protein construct was stable, non-host homologous, non-allergic, non-toxic, and elicit humoral and cellular responses. It has conformational B cell epitopes and potential to elicit IFN-γ, IL-4, and IL-10 secretion. Conclusions This novel recombinant multi-epitope protein constructed using the common epitopes from M. leprae and M. lepromatosis has a huge immunological potential, is stable, and can be lyophilized to be used in ELISA plates or even in biosensors, which are user-friendly diagnosis tools, facilitating translation into human sample tests.

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Development of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection

Cited by 7 publications

References 35 publications

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Susceptibility and resistance in leprosy: Studies in the mouse model

In silico designing of a recombinant multi-epitope antigen for leprosy diagnosis

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