Human immune responses to infective stage larval-specific chitinase of filarial parasite, Onchocerca volvulus, Ov-CHI-1.

Egerton, Gillian; McCarthy, James S.; Nutman, Thomas B.; Bianco, A. E.

doi:10.1186/1475-2883-2-6

Cited by 10 publications

(2 citation statements)

References 34 publications

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“…In 2003, the same group reported OvCHT1 as an antigen that strongly induces both humoral and cellular immune responses in humans. 57 Following such discoveries on OvCH1 roles, Gloeckner et al 55 conducted a screening against OvCHT1 using the Johns Hopkins Clinical Compound Library, which that contains over 1500 existing drugs. Closantel, already approved for veterinary uses, was identified as a potent and specific inhibitor of this filarial chitinase, with an IC 50 of 1.6 μM.…”

Section: Article In Pressmentioning

confidence: 99%

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

Sainas

Dosio

Boschi

et al. 2018

Annual Reports in Medicinal Chemistry

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The Parasite and Its Life Cycle 1.2 Clinical Presentation 2. Drugs and Drug Combinations in Clinical or Preclinical Evaluations 2.1 Diethylcarbamazine (DEC) 2.2 Ivermectin 2.3 Benzimidazole Drugs 2.4 Doxycycline 2.5 Rifampicin 2.6 Emodepside 2.7 Combination Therapy 3. Recent Advances Beyond Ivermectin 3.1 Searching for Chemodiversity within Natural Sources 3.2 The Repositioning of Closantel: Targeting OvCHT1 Chitinase 3.3 Studies on New Therapeutic O. volvus Targets 4. Methodologies for Onchocerciasis Diagnosis 4.1 Clinical Examination 4.2 Microscopic Identification of Microfilariae in Skin Snips 4.3 Nucleic Acid-Based Molecular Assays 4.4 Diethylcarbamazine Patch Test 4.5 Antibody Diagnostic Tests 5. Conclusions References

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Section: Article In Pressmentioning

confidence: 99%

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

Sainas

Dosio

Boschi

et al. 2018

Annual Reports in Medicinal Chemistry

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“…Immune host responses to antigens of the parasite micro lariae (mf), antigens of the adult worms or the parasite alone, result in various pathologies. These include dermatitis, atrophy of the skin, visual impairment, and blindness (Ward et al 1988; Wu et al 2003). The O. volvulus parasite has also been shown to exist in an endosymbiotic relationship with bacteria belonging to the genus Wolbachia (Kozek and Marroquin 1977).…”

Section: Introductionmentioning

confidence: 99%

Survival of worm masses of Onchocerca ochengi in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model

et al. 2023

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Onchocerciasis, the second leading infectious cause of blindness, a icts approximately 21 million people globally. Its control is limited to the use of the micro laricidal drugs, ivermectin and moxidectin.Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macro laricides that kill adult worms. The development of such drugs has been mired by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. change female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using 'proof-of-concept' studies, whether known macro laricidal drugs can kill these worms. Animals were surgically implanted with mechanical or enzyme-liberated O. change female worms, and sacri ced at various time points to test for survival. Recovered worms were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation, 58.6 ± 7.5% female worms were recovered from hamsters, and 20 ± 3.5% from gerbils. Those recovered from gerbils were mostly disintegrated or fragmented, with signi cantly higher fragmentation observed with enzymatically-liberated worms. FBZ had no signi cant effect on the number worms recovered, but enhanced embryo degradation in gerbils and reduced worm viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. change. The hamsters appeared to maintain the worms longer, compared to gerbils.

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ESTs analyses of Lampetra japonica liver and comparation transcriptome with the jawed vertebrates

Zhu

Yali

et al. 2008

Sci. China Ser. C-Life Sci.

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A cDNA library was constructed from the liver of Lampetra japonica. 10077 ESTs were obtained by random selecting clones for sequencing. The results demonstrated that 8515 ESTs were assembled into 648 consensus sequences, represented 2210 unique transcripts, 47.06% of which were predicted as full length cDNAs. In addition, 1562 ESTs were singlets. Using the BLAST to align the assembled ESTs, we found that 93.9% (2053) transcripts shared similarity to sequences published in GenBank databases. The functional annotations to assembled ESTs showed that the genes, involved in immunology, blood coagulation and metabolism of jawed vertebrates, were highly expressed in the liver of L. japonica. Furthermore, 8 potential novel genes were identified. Further comparing liver transcriptome of L. japonica with Fundulus heteroclitus, Mus musculus, Bos Taurus, and Homo sapiens revealed that the genes of Chitinase and Polysaccharides metabolism were more highly expressed in L. japonica than the others, which implied that they may play an important role in immunity of L. japonica. In addition, using the TargetScan, we marked microRNA target within 3' UTR of L. japonica liver transcriptome. The data indicated that some microRNA targets were homology with the targets embeded in human cancer genes. The result seems to provide a useful clue to the treatment of human cancer. Therefore, the present work will be an important resource for investigating the functional genomics and proteomics of L. japonica as well as evolution of vertebrates.

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Human immune responses to infective stage larval-specific chitinase of filarial parasite, Onchocerca volvulus, Ov-CHI-1.

Cited by 10 publications

References 34 publications

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

Survival of worm masses of Onchocerca ochengi in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model

ESTs analyses of Lampetra japonica liver and comparation transcriptome with the jawed vertebrates

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