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An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major

BACKGROUND: 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 t...

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Autores principales: Iniguez, Eva, Schocker, Nathaniel S., Subramaniam, Krishanthi, Portillo, Susana, Montoya, Alba L., Al-Salem, Waleed S., Torres, Caresse L., Rodriguez, Felipe, Moreira, Otacilio C., Acosta-Serrano, Alvaro, Michael, Katja, Almeida, Igor C., Maldonado, Rosa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673233/
https://www.ncbi.nlm.nih.gov/pubmed/29069089
http://dx.doi.org/10.1371/journal.pntd.0006039
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author Iniguez, Eva
Schocker, Nathaniel S.
Subramaniam, Krishanthi
Portillo, Susana
Montoya, Alba L.
Al-Salem, Waleed S.
Torres, Caresse L.
Rodriguez, Felipe
Moreira, Otacilio C.
Acosta-Serrano, Alvaro
Michael, Katja
Almeida, Igor C.
Maldonado, Rosa A.
author_facet Iniguez, Eva
Schocker, Nathaniel S.
Subramaniam, Krishanthi
Portillo, Susana
Montoya, Alba L.
Al-Salem, Waleed S.
Torres, Caresse L.
Rodriguez, Felipe
Moreira, Otacilio C.
Acosta-Serrano, Alvaro
Michael, Katja
Almeida, Igor C.
Maldonado, Rosa A.
author_sort Iniguez, Eva
collection PubMed
description BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection.
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spelling pubmed-56732332017-11-18 An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major Iniguez, Eva Schocker, Nathaniel S. Subramaniam, Krishanthi Portillo, Susana Montoya, Alba L. Al-Salem, Waleed S. Torres, Caresse L. Rodriguez, Felipe Moreira, Otacilio C. Acosta-Serrano, Alvaro Michael, Katja Almeida, Igor C. Maldonado, Rosa A. PLoS Negl Trop Dis Research Article BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection. Public Library of Science 2017-10-25 /pmc/articles/PMC5673233/ /pubmed/29069089 http://dx.doi.org/10.1371/journal.pntd.0006039 Text en © 2017 Iniguez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Iniguez, Eva
Schocker, Nathaniel S.
Subramaniam, Krishanthi
Portillo, Susana
Montoya, Alba L.
Al-Salem, Waleed S.
Torres, Caresse L.
Rodriguez, Felipe
Moreira, Otacilio C.
Acosta-Serrano, Alvaro
Michael, Katja
Almeida, Igor C.
Maldonado, Rosa A.
An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673233/
https://www.ncbi.nlm.nih.gov/pubmed/29069089
http://dx.doi.org/10.1371/journal.pntd.0006039
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