title: Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis.
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.
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, Ave. Itzaes #490 x 59, 97000 Mérida, Yucatán, Mexico.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Aguilar-Be
authors.forename: Renata
authors.initials: R
authors.lastname: da Silva Zardo
authors.forename: Edilma
authors.initials: E
authors.lastname: Paraguai de Souza
authors.forename: Gulnara Patrícia
authors.initials: GP
authors.lastname: Borja-Cabrera
authors.forename: Miguel
authors.initials: M
authors.lastname: Rosado-Vallado
authors.forename: Mirza
authors.initials: M
authors.lastname: Mut-Martin
authors.forename: Maria del Rosario
authors.initials: Mdel R
authors.lastname: García-Miss
authors.forename: Clarisa Beatriz
authors.initials: CB
authors.lastname: Palatnik de Sousa
authors.forename: Eric
authors.initials: E
authors.lastname: Dumonteil
mesh_terms: D000818:Animals; D007111:Immunity, Cellular / Q000276:immunology; D037102:Lectins / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D013997:Time Factors; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D037102:Lectins; D019444:Vaccines, DNA; C027112:fucose-binding lectin