posted on 2017-09-13, 00:00authored byAnna 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.