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Siena, Italy

Gianchecchi E.,Immunology and Pharmacotherapy Area | Gianchecchi E.,VisMederi srl | Fierabracci A.,Immunology and Pharmacotherapy Area
Autoimmunity Reviews | Year: 2015

Autoimmune disorders are increasing worldwide. Although their pathogenesis has not been elucidated yet, a complex interaction of genetic and environmental factors is involved in their onset.Toll-like receptors (TLRs) represent a family of pattern recognition receptors involved in the recognition and in the defense of the host from invading microorganisms. They sense a wide range of pathogen associated molecular patterns (PAMPs) deriving from metabolic pathways selective of bacterial, viral, fungal and protozoan microorganisms. TLR activation plays a critical role in the activation of the downstream signaling pathway by interacting and recruiting several adaptor molecules. Although TLRs are involved in the protection of the host, several studies suggest that, in certain conditions, they play a critical role in the pathogenesis of autoimmune diseases. We review the most recent advances showing a correlation between some single nucleotide polymorphisms or copy number variations in TLR genes or in adaptor molecules involved in TLR signaling and the onset of several autoimmune conditions, such as Type I diabetes, autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. In light of the foregoing we finally propose that molecules involved in TLR pathway may represent the targets for novel therapeutic treatments in order to stop autoimmune processes. © 2015 Elsevier B.V.

Manini I.,University of Siena | Domnich A.,University of Genoa | Amicizia D.,University of Genoa | Rossi S.,University of Siena | And 5 more authors.
Expert Review of Vaccines | Year: 2015

Conventional egg-based manufacturing technology for seasonal influenza vaccines has several drawbacks, including its inflexibility, reliance on egg supplies, risk of contamination, absence of growth of some isolates and egg-adaptive viral mutations that threaten vaccine matching. To overcome these limitations, cell culture-derived vaccines have been designed, including the trivalent inactivated vaccine Flucelvax®/Optaflu® (brand names in the US/EU, respectively). Flucelvax/Optaflu has gained wide regulatory approval and is currently implemented in several countries. Non-clinical studies have assuaged hypothetical concerns regarding oncogenicity and use in persons allergic to dogs. Ample clinical data suggest the non-inferiority of Flucelvax/Optaflu to egg-based vaccines in terms of immunogenicity, safety and tolerability, and it has fulfilled American and European mandatory requirements. Although Flucelvax/Optaflu is currently indicated only for adults and the elderly, pediatric data indicate its good immunogenicity and safety. This paper provides an update on the clinical development of Flucelvax/Optaflu, its seasonal trials and available post-marketing surveillance data. © 2015 Informa UK, Ltd.

Trombetta C.M.,University of Siena | Montomoli E.,University of Siena | Montomoli E.,VisMederi srl
Expert Review of Vaccines | Year: 2016

Vaccination is the most effective method of controlling seasonal influenza infections and preventing possible pandemic events. Although influenza vaccines have been licensed and used for decades, the potential correlates of protection induced by these vaccines are still a matter of discussion. Currently, inactivated vaccines are the most common and the haemagglutination inhibition antibody titer is regarded as an immunological correlate of protection and the best available parameter for predicting protection from influenza infection. However, the assay shows some limitations, such as its low sensitivity to B and avian strains and inter-laboratory variability. Additional assays and next-generation vaccines have been evaluated to overcome the limitations of the traditional serological techniques and to elicit broad immune responses, underlining the need to revise the current correlates of protection. The aim of this review is to provide an overview of the current scenario regarding the immunological evaluation and correlates of protection of influenza vaccines. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Gianchecchi E.,VisMederi srl | Fierabracci A.,Infectivology and Clinical Trials Area
Immunologic Research | Year: 2016

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the selective destruction of insulin-producing β cells as result of a complex interplay between genetic, stochastic and environmental factors in genetically susceptible individuals. An increasing amount of experimental data from animal models and humans has supported the role played by imbalanced gut microbiome in T1D pathogenesis. The commensal intestinal microbiota is fundamental for several physiologic mechanisms, including the establishment of immune homeostasis. Alterations in its composition have been correlated to changes in the gut immune system, including defective tolerance to food antigens, intestinal inflammation and enhanced gut permeability. Early findings reported differences in the intestinal microbiome of subjects affected by prediabetes or overt disease compared to healthy individuals. The present review focuses on microbiota-host homeostasis, its alterations, factors that influence microbiome composition and discusses their putative correlation with T1D development. Further studies are necessary to clarify the role played by microbiota modifications in the processes that cause enhanced permeability and the autoimmune mechanisms responsible for T1D onset. © 2016 Springer Science+Business Media New York

Ambati A.,Karolinska Institutet | Ambati A.,Karolinska University Hospital | Valentini D.,Karolinska Institutet | Valentini D.,Karolinska University Hospital | And 8 more authors.
Immunology | Year: 2015

A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine. © 2015 John Wiley & Sons Ltd.

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