Heterologous prime-boost vaccination with the LACK antigen protects against murine 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.
Dondji
Blaise
B
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Pérez-Jimenez
Eva
E
Goldsmith-Pestana
Karen
K
Esteban
Mariano
M
McMahon-Pratt
Diane
D
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology* / Q000494:pharmacology; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology* / Q000494:pharmacology; D016052:Protozoan Vaccines / Q000276:immunology* / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014409:Tumor Necrosis Factor-alpha; C093139:LACK antigen, Leishmania; D007371:Interferon-gamma