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*
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; and
Wellcome Trust Laboratories for Molecular Parasitology, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom
Vaccination against visceral leishmaniasis has received
limited attention compared with cutaneous leishmaniasis, although the
need for an effective vaccine against visceral leishmaniasis is
pressing. In this study, we demonstrate for the first time that a
recombinant stage-specific hydrophilic surface protein of
Leishmania donovani, recombinant hydrophilic acylated
surface protein B1 (HASPB1), is able to confer protection against
experimental challenge. Protection induced by rHASPB1 does not require
adjuvant and, unlike soluble Leishmania Ag + IL-12,
extends to the control of parasite burden in the spleen, an organ in
which parasites usually persist and are refractory to a broad range of
immunological and chemotherapeutic interventions. Both
immunohistochemistry (for IL-12p40) and enzyme-linked immunospot assay
(for IL-12p70) indicate that immunization with rHASPB1 results in IL-12
production by dendritic cells, although an analysis of Ab isotype
responses to rHASPB1 suggests that this response is not sufficient in
magnitude to induce a polarized Th1 response. Although both vaccinated
and control-infected mice have equivalent frequencies of
rHASPB1-specific CD4+ T cells producing IFN-
,
vaccine-induced protection correlates with the presence of
rHASPB1-specific, IFN-
-producing CD8+ T cells. Thus, we
have identified a novel vaccine candidate Ag for visceral
leishmaniasis, which appears to operate via a mechanism similar to that
previously associated with DNA vaccination.
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