Visceral leishmaniasis: A novel nuclear envelope protein ‘nucleoporins-93 (NUP-93)’ from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response

Singh, Manish Kumar; Jamal, Fauzia; Dubey, Amit Kumar; Shivam, Pushkar; Kumari, Shipra; Pushpanjali, .; Bordoloi, Chayanika; Narayan, Shyam; Das, Vidya Nand Rabi; Pandey, Krishna; Das, Pradeep; Singh, Shubhankar Kumar

doi:10.1016/j.cyto.2018.07.005

Cited by 10 publications

(9 citation statements)

References 55 publications

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“…Most of the proteins electroeluted in this study have been identified through MALDI MS/MS in earlier reports [24,29]. The role of these parasitic proteins in disease progression has been ascertained in mouse models from several previous studies [29][30][31][32][33][34][35]. The 31 kDa protein was identified as ATP synthase α chain of Leishmania [29].…”

Section: Discussionmentioning

confidence: 90%

“…The 31 kDa protein was identified as ATP synthase α chain of Leishmania [29]. ATP synthase complex subunits are functionally associated with the membrane and thus can be [29] 63 Glycoprotein [24] 72 Heat shock 70-related protein 1 mitochondrial precursor (HSP 70) [29] 91 β tubulin [29] 97 Not yet indentified from LAg/ may be nucleoporins-93 (NUP-93) [35] potential targets for drugs, diagnostic probes or vaccine components against Leishmania. A protein with a molecular weight of 34 kDa was identified in this study through mass spectrometry and recognized as a Leishmania analogue of the receptors of activated C kinase (LACK).…”

Section: Discussionmentioning

confidence: 99%

“…The 91 kDa protein showed homology with β-tubulin but did not show immunogenicity and protective immunity as compared to the other tubulins in the experimental L. donovani vaccine study [29]. The 97 kDa protein was recently identified in both promastigote and amastigote forms of parasite as nucleoporins 93 (NUP93) and found to be an immunoprophylactic agent against Leishmania [35]. Identification of key antigenic targets of the protective human immune response against VL is central to the development of an efficacious vaccine against Leishmania.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

et al. 2020

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Background Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. Results We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-γ and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

et al. 2020

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“…The 91 kDa polypeptide showed homology with btubulin but did not show immunogenicity and protective immunity as compared to the other tubulins in the experimental L. donovani vaccine study [29]. The 97 kDa protein was recently reported as nucleoporins 93 (NUP93) that presents in both promastigotes and amastigotes forms and studied as immunoprophylactic agent [35]. [36].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Ejazi

Ghosh

Bhattacharyya

et al. 2019

Preprint

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BackgroundVisceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. MethodsIn this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, humans PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins.ResultsWe found that 34 and 51 kDa fractions show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. ConclusionsThe present study accounts our search for new biomarkers for tests of clinical cure as well as effective immunoprophylactic candidates for VL vaccination.

show abstract

“…The 91 kDa protein showed homology with b-tubulin but did not show immunogenicity and protective immunity as compared to the other tubulins in the experimental L. donovani vaccine study [29]. The 97 kDa protein was recently reported as nucleoporins 93 (NUP93) that presents in both promastigotes and amastigotes forms and studied as an immunoprophylactic agent [35]. [36].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Ejazi

Ghosh

Bhattacharyya

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

show abstract

Visceral leishmaniasis: A novel nuclear envelope protein ‘nucleoporins-93 (NUP-93)’ from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response

Cited by 10 publications

References 55 publications

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

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