IL12 p35 and p40 subunit genes administered as pPAL plasmid constructs do not improve protection of pPAL-LACK vaccine against canine leishmaniasis

Alcolea, P.J. ; Alonso, A. ; Esteban, A. ; Peris, P. (Universidad de Zaragoza) ; Cortés, A. (Universidad de Zaragoza) ; Castillo, J.A. (Universidad de Zaragoza) ; Larraga, V.

Resumen: Leishmania infantum causes zoonotic visceral leishmaniasis (ZVL) in the Mediterranean basin and South America. The parasite has been shown to co-infect HIV patients and an outbreak in central Spain was reported in the last decade. Therfore, ZVL is a public health problem, dogs being the parasite’s reservoir. We have developed a DNA vaccine based on the L. infantum activated protein kinase A receptor (LACK) using different plasmid vectors and vaccinia virus strains as vehicles. Recently, we have generated an antibiotic resistance marker-free plasmid vector called pPAL. Homologous pPAL-LACK prime-boost vaccination protects Beagle dogs as well as a heterologous plasmid-virus regime. For both reasons, pPAL improves safety. IL12 was described to trigger Th1 response through IFN-¿ production in infected dogs, being a good candidate for cytokine therapy in conventional treatment-unresponsive dogs. Herein, we report a complete protection study in dogs through inoculation of genes encoding for the p35 and p40 subunits which compose canine IL12 in combination with the LACK gene. A homologous plasmid-plasmid regime using independent pPAL constructs for each gene was inoculated in a 15-day interval. The infectious challenge using L. infantum promastigotes was successful. The outcome was pPAL-LACK vaccine protection suppression by IL12 administration. The important implications of this finding are discussed in the manuscript.

Idioma: Inglés

DOI: 10.1371/journal.pone.0212136

Año: 2019

Publicado en: PloS one 14, 2 (2019), e0212136[18 pp]
ISSN: 1932-6203

Factor impacto JCR: 2.74 (2019)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 27 / 71 = 0.38 (2019) - Q2 - T2

Factor impacto SCIMAGO: 1.023 - Multidisciplinary (Q1)

Tipo y forma: Article (Published version)

Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Área Medicina y Cirugía Animal (Dpto. Patología Animal)