Person: Mas Zubiri, Alicia
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First Name
Alicia
Last Name
Mas Zubiri
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Sanidad Animal
Area
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6 results
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Item Alternative strategy for visceral leishmaniosis control: HisAK70-Salmonella Choleraesuis-pulsed dendritic cells(Comparative Immunology, Microbiology and Infectious Diseases, 2017) Carrión Herrero, Francisco Javier; Domínguez Bernal, Gustavo Ramón; Martínez Rodrigo, Abel; Mas Zubiri, Alicia; Blanco Gutiérrez, María Del Mar; Orden Gutiérrez, José Antonio; Fuente López, Ricardo De LaHere, we describe a novel approach that exploits an attenuated mutant of Salmonella enterica serovar Choleraesuis as carrier to deliver a plasmid encoding protein HisAK70. Subsequently, dendritic cells (DCs) were pulsed with this vaccine vector. The aim of this study was to evaluate the effectiveness of the prepared HisAK70-S. Choleraesuis-pulsed DCs (HisAK70-SAL DCs) against visceral leishmaniosis (VL). In our ex vivo model of infection, the prepared formulations could decrease parasite growth by up to 80% by augmenting the production of IL-12p40 and by reducing arginase activity (ARG). Also, BALB/c mice when immunised with this formulation showed significant reduction in parasite burden in both spleen (20% of reduction) and liver (75% of reduction). The balance of the immune ratios IFN-γ/IL-10, TNF-α/IL-10, and IgG2a/IgG1 reflected the acquisition of an improved resistant phenotype in HisAK70-SAL DCs vaccinated mice compared to control mice. Our results suggest that HisAK70-SAL DCs could be a promising alternative approach for vaccine delivery that has the potential to fight Leishmania infantum (L. infantum) infection.Item A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model(International Journal of Molecular Sciences, 2023) Mas Zubiri, Alicia; Hurtado Morillas, Clara; Martínez Rodrigo, Abel; Orden Gutiérrez, José Antonio; Fuente López, Ricardo De La; Domínguez Bernal, Gustavo Ramón; Carrión Herrero, Francisco JavierZoonotic leishmaniases are a worldwide public health problem for which the development of effective vaccines remains a challenge. A vaccine against leishmaniases must be safe and affordable and should induce cross-protection against the different disease-causing species. In this context, the DNA vaccine pHisAK70 has been demonstrated to induce, in a murine model, a resistant phenotype against L. major, L. infantum, and L. amazonensis. Moreover, a chimeric multiepitope peptide, HisDTC, has been obtained by in silico analysis from the histone proteins encoded in the DNA vaccine and has showed its ability to activate a potent CD4+ and CD8+ T-cell protective immune response in mice against L. infantum infection. In the present study, we evaluated the plasmid DNA vaccine pHisAK70 in comparison with the peptide HisDTC (with and without saponin) against L. major and L. infantum infection. Our preliminary results showed that both formulations were able to induce a potent cellular response leading to a decrease in parasite load against L. infantum. In addition, the DNA candidate was able to induce better lesion control in mice against L. major. These preliminary results indicate that both strategies are potentially effective candidates for leishmaniases control. Furthermore, it is important to carry out such comparative studies to elucidate which vaccine candidates are the most appropriate for further development.Item Strength and medium-term impact of HisAK70 immunization in dogs: Vaccine safety and biomarkers of effectiveness for ex vivo Leishmania infantum infection(Comparative Immunology, Microbiology and Infectious Diseases, 2019) Martínez Rodrigo, Abel; Mas Zubiri, Alicia; Fernández-Cotrina, Javier; Belinchón-Lorenzo, Silvia; Orden Gutiérrez, José Antonio; Arias, Pablo; Fuente López, Ricardo De La; Carrión Herrero, Francisco Javier; Domínguez Bernal, Gustavo RamónHisAK70 candidates have successfully been tested in cutaneous (CL) and visceral leishmaniosis (VL) mouse models. Here, we analyse different biomarkers in dog trials after a heterologous immunization strategy with a HisAK70 candidate (plasmid DNA plus adoptive transfer of peripheral blood-derived dendritic cells (DCs) pulsed with the same pathoantigen and CpG ODN as an adjuvant) to explore the antileishmanial activity in an ex vivo canine co-culture system in the presence of Leishmania infantum parasites. In the canine model, the heterologous HisAK70 vaccine could decrease the infection index in the DC-T cell co-culture system by up to 54% after 30 days and reach almost 67% after 100 days post-immunization, respectively, compared to those obtained in the control group of dogs. The observed security and potential to fight ex vivo L. infantum infection highlight a HisAK70 heterologous immunization strategy as a promising alternative to evaluate its effectiveness against canine VL.Item QUIMERA SINTÉTICA MULTIEPITÓPICA COMO VACUNA Y TRATAMIENTO FRENTE A LEISHMANIOSIS EN MAMÍFEROS(2022) Martínez Rodrigo, Abel; Mas Zubiri, Alicia; Carrión Herrero, Francisco Javier; Orden Gutiérrez, José Antonio; Fuente López, Ricardo De La; Domínguez Bernal, Gustavo Ramón; Universidad Complutense de MadridQuimera sintética multiepitópica como vacuna y tratamiento frente a leishmaniosis en mamíferos. La invención se refiere a quimeras sintéticas que incluyen 4 péptidos multiepitópicos frente a Leishmania. Cada uno de los péptidos se ha seleccionado de una proteína de Leishmania infantum. Se trata de las histonas nucleosomales H2A, H2B, H3 y H4. La invención también se refiere a una composición farmacéutica que incluye una de estas quimeras sintéticas. También se refiere a una vacuna profiláctica y/o terapéutica frente a Leishmania spp para su uso en mamíferos y, especialmente, en humana y en perros.Item HisAK70: progress towards a vaccine against different forms of leishmaniosis(2015) Carrión Herrero, Francisco Javier; Domínguez Bernal, Gustavo Ramón; Horcajo Iglesias, María Del Pilar; Orden Gutiérrez, José Antonio; Ruiz Santa Quiteria Serrano De La Cruz, José Antonio; Fuente López, Ricardo De La; Mas Zubiri, Alicia; Martínez Rodrigo, Abel; Ordóñez Gutiérrez, LaraBackground Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.Item Raccoons (Procyon lotor) in the Madrid region of Spain are carriers of antimicrobial‐resistant Escherichia coli and enteropathogenic E. coli(Zoonoses and Public Health, 2020) Orden Gutiérrez, José Antonio; García‐Meniño, Isidro; Flament‐Simon, Saskia C.; Blanco, Jorge; Francisco Sobrino; Fuente López, Ricardo De La; Martínez Rodrigo, Abel; Mas Zubiri, Alicia; Carrión Herrero, Francisco Javier; Domínguez Bernal, Gustavo Ramón; Sobrino, FranciscoThe role of wildlife in the epidemiology of antimicrobial resistance is unclear. Raccoons in North America can carry a variety of enteric bacteria, with associated antimicrobial resistance, that could infect humans and livestock. The potential for raccoons to carry these bacteria in Europe, where they are an invasive species, has not been explored. Our objectives were to determine the prevalence of Escherichia coli with associated antimicrobial resistance in raccoons from the Madrid region of Spain and to determine whether they are carriers of potential human pathogens, including verotoxin‐producing E. coli (VTEC) and enteropathogenic E. coli (EPEC). In total, we tested 237 E. coli isolates from the faeces of 83 euthanized raccoons for susceptibility to 14 antimicrobial agents and the presence of VTEC and EPEC. Antimicrobial resistance to at least one antimicrobial was detected in the faeces of 51% (42/83; 95% CI, 40.1–61.1) of the raccoons tested. A high percentage of raccoons carried, in their faeces, E. coli isolates resistant to ampicillin (33%), streptomycin (33%), tetracycline (30%), sulphafurazole (31%) and trimethoprim‐sulphamethoxazole (23%). We detected one isolate of extended‐spectrum β‐lactamase‐producing E. coli from the faeces of one raccoon. We detected VTEC in the faeces of one raccoon, and EPEC in the faeces of 12% (10/83) of the raccoons. Of the raccoons that carried EPEC in their faeces, 60% (6/10) carried EPEC isolates that exhibited characteristics associated with pathogenicity in humans. Raccoons in Madrid can carry pathogenic and antimicrobial‐resistant E. coli in their faeces and may be a risk to public health because of their potential to contaminate food and the environment with their faeces.