Dataset Information

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

ABSTRACT:

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 ?-galactopyranosyl (?-Gal) epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these ?-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 ?-Gal epitopes covalently attached to bovine serum albumin (BSA), as vaccine candidates against L. major, using ?1,3-galactosyltransferase-knockout (?1,3GalT-KO) mice. These transgenic mice, similarly to humans, do not express nonreducing, linear ?-Gal epitopes in their cells and are, therefore, capable of producing high levels of anti-?-Gal antibodies. We observed that Gal?(1,6)Gal?-BSA (NGP5B), but not Gal?(1,4)Gal?-BSA (NGP12B) or Gal?(1,3)Gal?-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-?-Gal antibodies and induction of Th1 cytokines.

Conclusions/significance

We propose that NGP5B is an attractive candidate for the study of potential synthetic ?-Gal-neoglycoprotein-based vaccines against L. major infection.

SUBMITTER: Iniguez E

PROVIDER: S-EPMC5673233 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Iniguez Eva E Schocker Nathaniel S NS Subramaniam Krishanthi K Portillo Susana S Montoya Alba L AL Al-Salem Waleed S WS Torres Caresse L CL Rodriguez Felipe F Moreira Otacilio C OC Acosta-Serrano Alvaro A Michael Katja K Almeida Igor C IC Maldonado Rosa A RA

PLoS neglected tropical diseases 20171025 10

<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 therap ...[more]

PMID: 29069089

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