Veramendi Charola, Jon
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Veramendi Charola
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Jon
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Agronomía, Biotecnología y Alimentación
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IMAB. Research Institute for Multidisciplinary Applied Biology
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Publication Open Access Human papillomavirus L1 protein expressed in tobacco chloroplasts self-assembles into virus-like particles that are highly immunogenic(Wiley, 2008) Fernández San Millán, Alicia; Martín Ortigosa, Susana; Hervás Stubbs, Sandra; Corral-Martínez, Patricia; Seguí-Simarro, José M.; Gaétan, Julien; Coursaget, Pierre; Veramendi Charola, Jon; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako InstitutuaCervical cancer is the second most prevalent cancer in women worldwide. It is linked to infection with human papillomavirus (HPV). As the virus cannot be propagated in culture, vaccines based on virus‐like particles have been developed and recently marketed. However, their high costs constitute an important drawback for widespread use in developing countries, where the incidence of cervical cancer is highest. In a search for alternative production systems, the major structural protein of the HPV‐16 capsid, L1, was expressed in tobacco chloroplasts. A very high yield of production was achieved in mature plants (~3 mg L1/g fresh weight; equivalent to 24% of total soluble protein). This is the highest expression level of HPV L1 protein reported in plants. A single mature plant synthesized ~240 mg of L1. The chloroplast‐derived L1 protein displayed conformation‐specific epitopes and assembled into virus‐like particles, visible by transmission electron microscopy. Furthermore, leaf protein extracts from L1 transgenic plants were highly immunogenic in mice after intraperitoneal injection, and neutralizing antibodies were detected. Taken together, these results predict a promising future for the development of a plant‐based vaccine against HPV.Publication Open Access A chloroplast-derived Toxoplasma gondiiGRA4 antigen used as an oral vaccine protects against toxoplasmosis in mice(Wiley, 2012) Yácono, María del L.; Farrán Blanch, Inmaculada; Becher, Melina L.; Sander, Valeria; Sánchez, Vanesa R.; Martín, Valentina; Veramendi Charola, Jon; Clemente, Marina; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako InstitutuaThe parasitic protozoan Toxoplasma gondii, the causal agent of toxoplasmosis, can infect most mammals and birds. In human medicine, T. gondii can cause complications in pregnant women and immunodeficient individuals, while in veterinary medicine, T. gondii infection has economic importance due to abortion and neonatal loss in livestock. Thus, the development of an effective anti‐Toxoplasma vaccine would be of great value. In this study, we analysed the expression of T. gondii GRA4 antigen by chloroplast transformation (chlGRA4) in tobacco plants and evaluated the humoral and cellular responses and the grade of protection after oral administration of chlGRA4 in a murine model. The Western blot analysis revealed a specific 34‐kDa band mainly present in the insoluble fractions. The chlGRA4 accumulation levels were approximately 6 μg/g of fresh weight (equivalent to 0.2% of total protein). Oral immunization with chlGRA4 resulted in a decrease of 59% in the brain cyst load of mice compared to control mice. ChlGRA4 immunization elicited both a mucosal immune response characterized by the production of specific IgA, and IFN‐γ, IL‐4 and IL‐10 secretion by mesenteric lymph node cells, and a systemic response in terms of GRA4‐specific serum antibodies and secretion of IFN‐γ, IL‐4 and IL‐10 by splenocytes. Our results indicate that oral administration of chlGRA4 promotes the elicitation of both mucosal and systemic balanced Th1/Th2 responses that control Toxoplasma infection, reducing parasite loads.