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Virus-like Particle Display of the α‑Gal Carbohydrate for Vaccination against Leishmania Infection
journal contributionposted on 2017-09-13, 00:00 authored by Anna Paula V. Moura, Luiza C. B. Santos, Carlos Ramon Nascimento Brito, Edward Valencia, Caroline Junqueira, Adalberto A. P. Filho, Mauricio R. V. Sant’Anna, Nelder F. Gontijo, Daniella C. Bartholomeu, Ricardo T. Fujiwara, Ricardo T. Gazzinelli, Craig S. McKay, Carlos A. Sanhueza, M. G. Finn, Alexandre Ferreira Marques
Secreted and surface-displayed carbohydrates are essential for virulence and viability of many parasites, including for immune system evasion. We have identified the α-Gal trisaccharide epitope on the surface of the protozoan parasites Leishmania infantum and Leishmania amazonensis, the etiological agents of visceral and cutaneous leishmaniasis, respectively, with the latter bearing larger amounts of α-Gal than the former. A polyvalent α-Gal conjugate on the immunogenic Qβ virus-like particle was tested as a vaccine against Leishmania infection in a C57BL/6 α-galactosyltransferase knockout mouse model, which mimics human hosts in producing high titers of anti-α-Gal antibodies. As expected, α-Gal-T knockout mice infected with promastigotes of both Leishmania species showed significantly lower parasite load in the liver and slightly decreased levels in the spleen, compared with wild-type mice. Vaccination with Qβ–α-Gal nanoparticles protected the knockout mice against Leishmania challenge, eliminating the infection and proliferation of parasites in the liver and spleen as probed by qPCR. The α-Gal epitope may therefore be considered as a vaccine candidate to block human cutaneous and visceral leishmaniasis.
parasite loadα- GalLeishmania speciesC 57BL α- galactosyltransferase knockout mouse modelLeishmania Infection Secretedsystem evasionLeishmania amazonensisknockout miceα- Gal trisaccharide epitopecutaneous leishmaniasispolyvalent α- Gal conjugateparasites Leishmania infantumimmunogenic Q β virus-like particleetiological agentsα- Gal epitopeLeishmania infectionwild-type micevaccine candidateα- Gal-T knockout micesurface-displayed carbohydratesLeishmania challengeVirus-like Particle Display-α-Gal antibodies