Hervás Stubbs, Sandra

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https://academica-e.unavarra.es/handle/2454/49243

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Hervás Stubbs

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Sandra

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Ciencias de la Salud

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1175452

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2320

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    PublicationOpen 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 Institutua
    Cervical 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.
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    PublicationOpen Access
    Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
    (Wiley, 2023) Basurco, Leyre; Abellanas, Miguel Ángel; Ayerra, Leyre; Conde, Enrique; Vinueza-Gavilanes, Rodrigo; Luquin, Esther; Vales, Africa; Vilas, Amaia; San Martin-Uriz, Patxi; Tamayo Uria, Ibon; Alonso Roldán, Marta; Hernaez, Mikel; González-Aseguinolaza, Gloria; Clavero Ibarra, Pedro Luis; Mengual, Elisa; Arrasate, Montserrat; Hervás Stubbs, Sandra; Aymerich, María Soledad; Ciencias de la Salud; Osasun Zientziak
    Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro-inflammatory stimulus was different. In this study, we assessed the innate immune reaction in the midbrain and in the striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing the alpha-synuclein and mCherry genes or the mCherry gene was administered into the substantia nigra. Myeloid cells (CD11b(+)) and astrocytes (ACSA2(+)) were purified from the midbrain and striatum for bulk RNA sequencing. In the parkinsonian midbrain, CD11b(+) cells presented a unique anti-inflammatory transcriptomic profile that differed from degenerative microglia signatures described in experimental models for other neurodegenerative conditions. By contrast, striatal CD11b(+) cells showed a pro-inflammatory state and were similar to disease-associated microglia. In the midbrain, a prominent increase of infiltrated monocytes/macrophages was observed and, together with microglia, participated actively in the phagocytosis of dopaminergic neuronal bodies. Although striatal microglia presented a phagocytic transcriptomic profile, morphology and cell density was preserved and no active phagocytosis was detected. Interestingly, astrocytes presented a pro-inflammatory fingerprint in the midbrain and a low number of differentially displayed transcripts in the striatum. During alpha-synuclein-dependent degeneration, microglia and astrocytes experience context-dependent activation states with a different contribution to the inflammatory reaction. Our results point towards the relevance of selecting appropriate cell targets to design neuroprotective strategies aimed to modulate the innate immune system during the active phase of dopaminergic degeneration.
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    PublicationOpen Access
    Evaluation of a Salmonella strain lacking the secondary messenger c-di-GMP and RpoS as a live oral vaccine
    (Public Library of Science, 2016) Latasa Osta, Cristina; Echeverz Sarasúa, Maite; García Ona, Enrique; Burgui Erice, Saioa; Casares, Noelia; Hervás Stubbs, Sandra; Lasarte, Juan José; Lasa Uzcudun, Íñigo; Solano Goñi, Cristina; García Martínez, Begoña; Gil Puig, Carmen; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua; Gobierno de Navarra / Nafarroako Gobernua: IIM 13329.RI1
    Salmonellosis is one of the most important bacterial zoonotic diseases transmitted through the consumption of contaminated food, with chicken and pig related products being key reservoirs of infection. Although numerous studies on animal vaccination have been performed in order to reduce Salmonella prevalence, there is still a need for an ideal vaccine. Here, with the aim of constructing a novel live attenuated Salmonella vaccine candidate, we firstly analyzed the impact of the absence of cyclic-di-GMP (c-di-GMP) in Salmonella virulence. Cdi-GMP is an intracellular second messenger that controls a wide range of bacterial processes, including biofilm formation and synthesis of virulence factors, and also modulates the host innate immune response. Our results showed that a Salmonella multiple mutant in the twelve genes encoding diguanylate cyclase proteins that, as a consequence, cannot synthesize c-di-GMP, presents a moderate attenuation in a systemic murine infection model. An additional mutation of the rpoS gene resulted in a synergic attenuating effect that led to a highly attenuated strain, referred to as ΔXIII, immunogenic enough to protect mice against a lethal oral challenge of a S. Typhimurium virulent strain. ΔXIII immunogenicity relied on activation of both antibody and cell mediated immune responses characterized by the production of opsonizing antibodies and the induction of significant levels of IFN-γ, TNF- α, IL-2, IL-17 and IL-10. ΔXIII was unable to form a biofilm and did not survive under desiccation conditions, indicating that it could be easily eliminated from the environment. Moreover, ΔXIII shows DIVA features that allow differentiation of infected and vaccinated animals. Altogether, these results show ΔXIII as a safe and effective live DIVA vaccine