Cross-Protective Efficacy of a Prophylactic
Leishmania donovani
DNA Vaccine against Visceral and Cutaneous Murine Leishmaniasis
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Published:2005-02
Issue:2
Volume:73
Page:812-819
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ISSN:0019-9567
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Container-title:Infection and Immunity
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language:en
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Short-container-title:Infect Immun
Author:
Aguilar-Be Ingrid1, da Silva Zardo Renata2, Paraguai de Souza Edilma2, Borja-Cabrera Gulnara Patrícia2, Rosado-Vallado Miguel1, Mut-Martin Mirza3, del Rosario García-Miss Maria3, Palatnik de Sousa Clarisa Beatriz2, Dumonteil Eric1
Affiliation:
1. Laboratorio de Parasitología 2. Instituto de Microbiologia “Professor Paulo de Góes,” Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 3. Laboratorio de Inmunobiología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi,” Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
Abstract
ABSTRACT
The fucose-mannose ligand (FML) complex of
Leishmania donovani
is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (
L. chagasi
) and cutaneous (
L. mexicana
) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with
L. chagasi
, whereas no differences were observed between vaccine and control groups after infection with
L. mexicana
. A strong intradermal reaction to
L. donovani
and
L. mexicana
antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against
L. donovani
antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against
L. chagasi
infection with reductions in parasite loads of 79%. FML also conferred partial protection against
L. mexicana
infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in
L. chagasi
parasite load and a 65% reduction in
L. mexicana
lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4
+
T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several
Leishmania
species.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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