Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.
<h4>Background</h4>There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ w...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001874&type=printable |
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| author | Om Prakash Singh Carmel B Stober Abhishek Kr Singh Jenefer M Blackwell Shyam Sundar |
| author_facet | Om Prakash Singh Carmel B Stober Abhishek Kr Singh Jenefer M Blackwell Shyam Sundar |
| author_sort | Om Prakash Singh |
| collection | DOAJ |
| description | <h4>Background</h4>There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations.<h4>Methods</h4>Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC).<h4>Results</h4>Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects.<h4>Conclusions</h4>Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates. |
| format | Article |
| id | doaj-art-ae0dfbe099bd4dbd97d2c8b091fee241 |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-ae0dfbe099bd4dbd97d2c8b091fee2412025-08-20T02:15:23ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352012-01-01610e187410.1371/journal.pntd.0001874Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.Om Prakash SinghCarmel B StoberAbhishek Kr SinghJenefer M BlackwellShyam Sundar<h4>Background</h4>There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations.<h4>Methods</h4>Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC).<h4>Results</h4>Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects.<h4>Conclusions</h4>Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001874&type=printable |
| spellingShingle | Om Prakash Singh Carmel B Stober Abhishek Kr Singh Jenefer M Blackwell Shyam Sundar Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. PLoS Neglected Tropical Diseases |
| title | Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. |
| title_full | Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. |
| title_fullStr | Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. |
| title_full_unstemmed | Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. |
| title_short | Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. |
| title_sort | cytokine responses to novel antigens in an indian population living in an area endemic for visceral leishmaniasis |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001874&type=printable |
| work_keys_str_mv | AT omprakashsingh cytokineresponsestonovelantigensinanindianpopulationlivinginanareaendemicforvisceralleishmaniasis AT carmelbstober cytokineresponsestonovelantigensinanindianpopulationlivinginanareaendemicforvisceralleishmaniasis AT abhishekkrsingh cytokineresponsestonovelantigensinanindianpopulationlivinginanareaendemicforvisceralleishmaniasis AT jenefermblackwell cytokineresponsestonovelantigensinanindianpopulationlivinginanareaendemicforvisceralleishmaniasis AT shyamsundar cytokineresponsestonovelantigensinanindianpopulationlivinginanareaendemicforvisceralleishmaniasis |