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Heterologous Prime-Boost Vaccination with the LACK Antigen Protects against Murine Visceral Leishmaniasis

Dondji, Blaise, Pérez-Jimenez, Eva, Goldsmith-Pestana, Karen, Esteban, Mariano, McMahon-Pratt, Diane
Infection and immunity 2005 v.73 no.8 pp. 5286-5289
DNA, Leishmania infantum, Vaccinia virus, antigens, humans, interferon-gamma, liver, lymph nodes, lymphotoxin, mice, parasites, receptors, spleen, tumor necrosis factor-alpha, vaccination, viruses, visceral leishmaniasis
This study reports the efficacy of a heterologous prime-boost vaccination using DNA and vaccinia viruses (Western Reserve [WR] virus and modified [attenuated] vaccinia virus Ankara [MVA]) expressing the LACK antigen (Leishmania homologue of receptors for activated C kinase) and an intradermal murine infection model employing Leishmania infantum. At 1 month postinfection, vaccinated mice showed high levels of protection in the draining lymph node (240-fold reduction in parasite burden) coupled with significant levels of gamma interferon (20 to 200 ng/ml) and tumor necrosis factor alpha/lymphotoxin (8 to 134 pg/ml). Significant but lower levels of protection (6- to 30-fold) were observed in the spleen and liver. Comparable levels of protection were found for mice boosted with either LACK-WR or LACK-MVA, supporting the use of an attenuated vaccinia virus-based vaccine against human visceral leishmaniasis.