Protamine Nanocapsules for the Development of Thermostable Adjuvanted Nanovaccines.

One of the main challenges in the development of vaccine has been to improve their stability at room temperature and eliminate the limitations associated with the cold chain storage. In this paper, we describe the development and optimization of thermostable nanocarriers consisting of an oily core with immunostimulating activity, containing squalene or α tocopherol surrounded by a protamine shell. The results showed that these nanocapsules can efficiently associate the recombinant hepatitis B surface antigen (rHBsAg) without compromising its antigenicity. Furthermore, the freeze-dried protamine nanocapsules were able to preserve the integrity and bioactivity of the associated antigen upon storage for at least 12 months at room temperature. In vitro studies evidenced the high internalization of the nanocapsules by immunocompetent cells, followed by cytokine secretion and complement activation. In vivo studies showed the capacity of rHBsAg-loaded nanocapsules to elicit protective levels upon intramuscular or intranasal administration to mice. Overall, our data indicate that protamine nanocapsules are an innovative thermostable nanovaccine platform for improved antigen delivery.

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Bilayer polymeric nanocapsules: A formulation approach for a thermostable and adjuvanted E. coli antigen vaccine.

One of the strategies used to improve the immunogenicity of purified protein antigens has relied on their association with synthetic nanocarriers, which, in general, have functioned as simple antigen containers. Here, we present a more advanced strategy based on the design of an antigen nanocarrier at the molecular level. The nanocarrier is composed of a vitamin E oily core, surrounded by two layers: a first layer of chitosan and a second of dextran sulphate. The selected antigen, IutA protein from Escherichia coli, was harboured between the two polymeric layers. The final bilayer nanocapsules had a nanometric size (≈ 200 nm), a negative zeta potential (< -40 mV) and a good antigen association efficiency (≈ 70%). The bilayer architecture led to an improvement on the formulation stability and the controlled release of the associated antigen. Remarkably, after being administered to mice, bilayer nanocapsules elicited higher IgG levels than those obtained with antigen precipitated with Alum. Moreover, freeze-dried nanocapsules were stable at room temperature for, at least, 3 months. These promising data, in addition to their contribution to the development of an uropathogenic E. coli vaccine, has allowed us to validate these novel bilayer nanocapsules as adequate platforms for the delivery of protein antigens.

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB.

In recent years, there has been an increase in the production of several types of nanoparticles (Nps) for different purposes. Several studies have been performed to analyse the toxicity induced by some of these individual Nps, but data are scarce on the potential hazards or beneficial effects induced by a range of nanomaterials in the same environment. The purpose of the study described here was to evaluate the toxicological effects induced by in vitro exposure of human cells to ZnO Nps in combination with different concentrations of other metal oxide Nps (Al2O3, CeO2, TiO2 and Y2O3). The results indicate that the presence of these Nps has synergistic or antagonistic effects on the cell death induced by ZnO Nps, with a quite marked beneficial effect observed when high concentrations of Nps were tested. Moreover, analysis by Western blot of the main components of the intracellular activation routes (MAPKs and NFκB) again showed that the presence of other Nps can affect cell activation. In conclusion, the presence of several Nps in the same environment modifies the functional activity of one individual Np. Further studies are required in order to elucidate the effects induced by combinations of nanomaterials.

Cytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship.

INTRODUCTION: Schizophrenia is a multifactorial psychiatric disease with complex interactions among the brain and the immune system. A psycho-immune relationship underling schizophrenia is supported by several studies and integrates a specific area of knowledge - psychoneuroimmunology. METHODS: A systematic review was performed by 2009 Preferred Reporting Items (PRISMA) recommendations. Based on the inclusion/exclusion criteria, publications with relevant information (evaluated by the Joanna Briggs Institute Critical Appraisals tools to quality assessment) were included. RESULTS: In this review, we considered the inflammatory activity promoted by cytokine alterations in schizophrenia aetiology, which reflects the systemic comprehension of this disease in opposition to the traditional approach focused solely on the brain. We focus on the analysis of several specific outcomes, such as proinflammatory cytokines, sample sort, laboratory techniques, diagnosis scales and results of each publication. CONCLUSION: This systematic review confirms the existence of cytokines abnormalities in schizophrenia disease. Immune imbalances such as increased levels of some cytokines (either at protein level or at mRNA expression), cytokine mRNAs, as well as cytokine gene polymorphisms have been reported with a large support in schizophrenia. These findings provide a strong evidence of a concomitant process of inflammatory activity in schizophrenia illness course.

Protamine-based nanoparticles as new antigen delivery systems.

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.