RT Journal Article T1 Mitigating an undesirable immune response of inherent susceptibility to cutaneous leishmaniosis in a mouse model: the role of the pathoantigenic HISA70 DNA vaccine A1 Domínguez Bernal, Gustavo Ramón A1 Horcajo Iglesias, María Del Pilar A1 Orden Gutiérrez, José Antonio A1 Fuente López, Ricardo De La A1 Herrero Gil, Aldara A1 Ordóñez Gutiérrez, Lara A1 Carrión Herrero, Francisco Javier AB Leishmania major is the major cause of cutaneous leishmaniosis (CL) outside of the Americas. In the present study we have cloned six Leishmania genes (H2A, H2B, H3, H4, A2 and HSP70) into the eukaryotic expression vector pCMVβ-m2a, resulting in pCMV-HISA70m2A, which encodes all six pathoantigenic proteins as a single polyprotein. This expression plasmid has been evaluated as a novel vaccine candidate in the BALB/c mouse model of CL. The DNA vaccine shifted the immune response normally induced by L. major infection away from a Th2-specific pathway to one of basal susceptibility. Immunization with pCMV-HISA70m2A dramatically reduced footpad lesions and lymph node parasite burdens relative to infected control mice. Complete absence of visceral parasite burden was observed in all 12 immunized animals but not in any of the 24 control mice. Moreover, vaccinated mice produced large amounts of IFN-γ, IL-17 and NO at 7 weeks post-infection (pi), and they showed lower arginase activity at the site of infection, lower IL-4 production and a weaker humoral immune response than infected control mice. Taken together, these results demonstrate the ability of the HISA70 vaccine to shift the murine immune response to L. major infection away from an undesirable, Th2-specific pathway to a less susceptible-like pathway involving Th1 and Th17 cytokine profiles. PB BioMed Central SN 1297-9716 YR 2012 FD 2012-08-09 LK https://hdl.handle.net/20.500.14352/92574 UL https://hdl.handle.net/20.500.14352/92574 LA eng NO Domínguez Bernal, G., Horcajo Iglesias, M. P., Orden Gutiérrez, J. A. et al. «Mitigating an Undesirable Immune Response of Inherent Susceptibility to Cutaneous Leishmaniosis in a Mouse Model: The Role of the Pathoantigenic HISA70 DNA Vaccine». Veterinary Research, vol. 43, n.o 1, diciembre de 2012, p. 59. DOI.org (Crossref), https://doi.org/10.1186/1297-9716-43-59. NO Ministerio de Educación, Formación Profesional y Deportes (España) NO Universidad Complutense de Madrid/Banco de Santander DS Docta Complutense RD 5 abr 2025