Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?
Background CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibod...
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Online Access: | https://doi.org/10.1371/journal.pntd.0011776 https://doaj.org/article/8f4a6282c64b43338e1ba2c7e6ff355a |
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ftdoajarticles:oai:doaj.org/article:8f4a6282c64b43338e1ba2c7e6ff355a 2024-01-14T10:05:07+01:00 Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? Eglal I Amer Sonia R Allam Aceel Y Hassan Esmail M El-Fakharany Mona M Agwa Sherine N Khattab Eman Sheta Marwa H El-Faham 2023-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011776 https://doaj.org/article/8f4a6282c64b43338e1ba2c7e6ff355a EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011776&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011776 https://doaj.org/article/8f4a6282c64b43338e1ba2c7e6ff355a PLoS Neglected Tropical Diseases, Vol 17, Iss 12, p e0011776 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011776 2023-12-17T01:40:50Z Background CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. Methodology/principal findings We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. Conclusion/significance The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 12 e0011776 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Eglal I Amer Sonia R Allam Aceel Y Hassan Esmail M El-Fakharany Mona M Agwa Sherine N Khattab Eman Sheta Marwa H El-Faham Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. Methodology/principal findings We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. Conclusion/significance The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of ... |
format |
Article in Journal/Newspaper |
author |
Eglal I Amer Sonia R Allam Aceel Y Hassan Esmail M El-Fakharany Mona M Agwa Sherine N Khattab Eman Sheta Marwa H El-Faham |
author_facet |
Eglal I Amer Sonia R Allam Aceel Y Hassan Esmail M El-Fakharany Mona M Agwa Sherine N Khattab Eman Sheta Marwa H El-Faham |
author_sort |
Eglal I Amer |
title |
Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
title_short |
Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
title_full |
Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
title_fullStr |
Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
title_full_unstemmed |
Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
title_sort |
can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni? |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011776 https://doaj.org/article/8f4a6282c64b43338e1ba2c7e6ff355a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 12, p e0011776 (2023) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011776&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011776 https://doaj.org/article/8f4a6282c64b43338e1ba2c7e6ff355a |
op_doi |
https://doi.org/10.1371/journal.pntd.0011776 |
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PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
12 |
container_start_page |
e0011776 |
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