An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major.
Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic h...
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ftdoajarticles:oai:doaj.org/article:416f955864b947b18fcb34d17a0613fa 2023-05-15T15:12:45+02:00 An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. Eva Iniguez Nathaniel S Schocker Krishanthi Subramaniam Susana Portillo Alba L Montoya Waleed S Al-Salem Caresse L Torres Felipe Rodriguez Otacilio C Moreira Alvaro Acosta-Serrano Katja Michael Igor C Almeida Rosa A Maldonado 2017-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006039 https://doaj.org/article/416f955864b947b18fcb34d17a0613fa EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5673233?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006039 https://doaj.org/article/416f955864b947b18fcb34d17a0613fa PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0006039 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006039 2022-12-31T11:42:42Z Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic human vaccine available for L. major CL, and existing drug treatments are expensive, have toxic side effects, and resistant parasite strains have been reported. Hence, further therapeutic interventions against the disease are necessary. Terminal, non-reducing, and linear α-galactopyranosyl (α-Gal) epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these α-Gal epitopes in human cells makes these glycans highly immunogenic and thus potential targets for vaccine development against CL.Here, we evaluated three neoglycoproteins (NGPs), containing synthetic α-Gal epitopes covalently attached to bovine serum albumin (BSA), as vaccine candidates against L. major, using α1,3-galactosyltransferase-knockout (α1,3GalT-KO) mice. These transgenic mice, similarly to humans, do not express nonreducing, linear α-Gal epitopes in their cells and are, therefore, capable of producing high levels of anti-α-Gal antibodies. We observed that Galα(1,6)Galβ-BSA (NGP5B), but not Galα(1,4)Galβ-BSA (NGP12B) or Galα(1,3)Galα-BSA (NGP17B), was able to significantly reduce the size of footpad lesions by 96% in comparison to control groups. Furthermore, we observed a robust humoral and cellular immune response with production of high levels of protective lytic anti-α-Gal antibodies and induction of Th1 cytokines.We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 10 e0006039 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
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 Eva Iniguez Nathaniel S Schocker Krishanthi Subramaniam Susana Portillo Alba L Montoya Waleed S Al-Salem Caresse L Torres Felipe Rodriguez Otacilio C Moreira Alvaro Acosta-Serrano Katja Michael Igor C Almeida Rosa A Maldonado An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic human vaccine available for L. major CL, and existing drug treatments are expensive, have toxic side effects, and resistant parasite strains have been reported. Hence, further therapeutic interventions against the disease are necessary. Terminal, non-reducing, and linear α-galactopyranosyl (α-Gal) epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these α-Gal epitopes in human cells makes these glycans highly immunogenic and thus potential targets for vaccine development against CL.Here, we evaluated three neoglycoproteins (NGPs), containing synthetic α-Gal epitopes covalently attached to bovine serum albumin (BSA), as vaccine candidates against L. major, using α1,3-galactosyltransferase-knockout (α1,3GalT-KO) mice. These transgenic mice, similarly to humans, do not express nonreducing, linear α-Gal epitopes in their cells and are, therefore, capable of producing high levels of anti-α-Gal antibodies. We observed that Galα(1,6)Galβ-BSA (NGP5B), but not Galα(1,4)Galβ-BSA (NGP12B) or Galα(1,3)Galα-BSA (NGP17B), was able to significantly reduce the size of footpad lesions by 96% in comparison to control groups. Furthermore, we observed a robust humoral and cellular immune response with production of high levels of protective lytic anti-α-Gal antibodies and induction of Th1 cytokines.We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection. |
format |
Article in Journal/Newspaper |
author |
Eva Iniguez Nathaniel S Schocker Krishanthi Subramaniam Susana Portillo Alba L Montoya Waleed S Al-Salem Caresse L Torres Felipe Rodriguez Otacilio C Moreira Alvaro Acosta-Serrano Katja Michael Igor C Almeida Rosa A Maldonado |
author_facet |
Eva Iniguez Nathaniel S Schocker Krishanthi Subramaniam Susana Portillo Alba L Montoya Waleed S Al-Salem Caresse L Torres Felipe Rodriguez Otacilio C Moreira Alvaro Acosta-Serrano Katja Michael Igor C Almeida Rosa A Maldonado |
author_sort |
Eva Iniguez |
title |
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
title_short |
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
title_full |
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
title_fullStr |
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
title_full_unstemmed |
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. |
title_sort |
α-gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by leishmania major. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0006039 https://doaj.org/article/416f955864b947b18fcb34d17a0613fa |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0006039 (2017) |
op_relation |
http://europepmc.org/articles/PMC5673233?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006039 https://doaj.org/article/416f955864b947b18fcb34d17a0613fa |
op_doi |
https://doi.org/10.1371/journal.pntd.0006039 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
10 |
container_start_page |
e0006039 |
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1766343390707843072 |