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



Iniguez, Eva, Schocker, Nathaniel S, Subramaniam, Krishanthi ORCID: 0000-0002-1734-9351, Portillo, Susana, Montoya, Alba L, Al-Salem, Waleed S, Torres, Caresse L, Rodriguez, Felipe, Moreira, Otacilio C, Acosta-Serrano, Alvaro
et al (show 3 more authors) (2017) An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by <i>Leishmania major</i>. PLOS NEGLECTED TROPICAL DISEASES, 11 (10). e0006039-.

Access the full-text of this item by clicking on the Open Access link.

Abstract

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection.

Item Type: Article
Uncontrolled Keywords: CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Animals, Mice, Knockout, Humans, Mice, Leishmania major, Leishmaniasis, Cutaneous, Galactosyltransferases, Glycoproteins, Galactosides, Epitopes, Gene Expression Regulation, Enzymologic, Leishmaniasis Vaccines, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 12 Aug 2019 13:55
Last Modified: 07 Oct 2023 02:28
DOI: 10.1371/journal.pntd.0006039
Open Access URL: https://journals.plos.org/plosntds/article/file?id...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3051539