title: Vaccination with leishmania hemoglobin receptor-encoding DNA protects against visceral leishmaniasis.
abstract: Leishmaniasis is a severe infectious disease. Drugs used for leishmaniasis are very toxic, and no vaccine is available. We found that the hemoglobin receptor (HbR) of Leishmania was conserved across various strains of Leishmania, and anti-HbR antibody could be detected in kala-azar patients' sera. Our results showed that immunization with HbR-DNA induces complete protection against virulent Leishmania donovani infection in both BALB/c mice and hamsters. Moreover, HbR-DNA immunization stimulated the production of protective cytokines like interferon-γ (IFN-γ), interleukin-12 (IL-12), and tumor necrosis factor-α (TNF-α) with concomitant down-regulation of disease-promoting cytokines like IL-10 and IL-4. HbR-DNA vaccination also induced a protective response by generating multifunctional CD4(+) and CD8(+) T cells. All HbR-DNA-vaccinated hamsters showed sterile protection and survived during an experimental period of 8 months. These findings demonstrate the potential of HbR as a vaccine candidate against visceral leishmaniasis.
authors.affiliation: Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Guha
authors.forename: Deepika
authors.initials: D
authors.lastname: Gupta
authors.forename: Ruchir
authors.initials: R
authors.lastname: Rastogi
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Vikram
authors.forename: Ganga
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Sanjiva
authors.initials: S
authors.lastname: Bimal
authors.forename: Syamal
authors.initials: S
authors.lastname: Roy
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D017124:Conserved Sequence; D006224:Cricetinae / Q000276:immunology / Q000469:parasitology; D004247:DNA / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D007074:Immunoglobulin G; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D004247:DNA