Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus.

Molecular characterization of human adenoviruses in urban wastewaters using next generation and Sanger sequencing.

Human adenoviruses (HAdVs) are of major public health importance and are associated with a variety of clinical manifestations, including gastroenteritis, respiratory, ocular and urinary tract infections. To study the occurrence, prevalence and diversity of HAdV species and types circulating in Italy, we conducted a large-scale molecular-epidemiological investigation, a yearlong monitoring of 22 wastewater treatment plants, covering 10 Italian regions, representative of northern, central, and southern Italy. A total of 141 raw sewage samples were collected from January to December 2013, and processed to detect and characterize by phylogenetic analysis a fragment of the hexon coding region of HAdVs.

The nature of the conserved basic amino acid sequences found among 437 heparin binding proteins determined by network analysis.

In multicellular organisms, a large number of proteins interact with the polyanionic polysaccharides heparan sulphate (HS) and heparin. These interactions are usually assumed to be dominated by charge-charge interactions between the anionic carboxylate and/or sulfate groups of the polysaccharide and cationic amino acids of the protein. A major question is whether there exist conserved amino acid sequences for HS/heparin binding among these diverse proteins.

Mucosal Antibodies to the C Terminus of Toxin A Prevent Colonization of Clostridium difficile.

Mucosal immunity is considered important for protection against infection (CDI). We show that in hamsters immunized with spores expressing a carboxy-terminal segment (TcdA) of toxin A, no colonization occurs in protected animals when challenged with strain 630. In contrast, animals immunized with toxoids showed no protection and remained fully colonized.

Antibody-mediated depletion of immunosuppressive factors from ovarian carcinoma-associated ascites for investigation of paracrine versus autocrine effects.

Many studies seek to explore the impact of extrinsic soluble factors present in serum, interstitial fluids or cell-conditioned media on cells in vitro. A convenient approach to elucidate the effects of a particular factor is its selective neutralization. However, intrinsic production of soluble factors such as cytokines by the cultured cells is common and can have an impact via autocrine mechanisms.

Workshop report: Malaria vaccine development in Europe--preparing for the future.

The deployment of a safe and effective malaria vaccine will be an important tool for the control of malaria and the reduction in malaria deaths. With the launch of the 2030 Malaria Vaccine Technology Roadmap, the malaria community has updated the goals and priorities for the development of such a vaccine and is now paving the way for a second phase of malaria vaccine development. During a workshop in Brussels in November 2014, hosted by the European Vaccine Initiative, key players from the European, North American and African malaria vaccine community discussed European strategies for future malaria vaccine development in the global context.

Heparan sulfate and heparin interactions with proteins.

Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissue-specific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them.

Russian vaccines against especially dangerous bacterial pathogens.

In response to the epidemiological situation, live attenuated or killed vaccines against anthrax, brucellosis, cholera, glanders, plague and tularemia were developed and used for immunization of at-risk populations in the Former Soviet Union. Certain of these vaccines have been updated and currently they are used on a selective basis, mainly for high risk occupations, in the Russian Federation. Except for anthrax and cholera these vaccines currently are the only licensed products available for protection against the most dangerous bacterial pathogens.

Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.

Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes.

Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers.

Rationale: Baseline circulating concentrations of C-reactive protein (CRP) are significantly associated with cardiovascular disease risk in general populations. This modest association has been inappropriately conflated with causality, and it has been claimed that CRP is proatherogenic. Most of the known causative factors for atherosclerosis stimulate increased CRP production, but comprehensive genetic epidemiology studies provide no support for a pathogenic role of CRP.

Sourcing and using stem cell lines for radiation research: Potential, challenges and good stem cell culture practice.

Purpose: Exposition of best practice in management and experimental use of human stem cell lines in radiobiological research. This paper outlines the key challenges to be addressed by radiobiologists wishing to use human pluripotent stem cell (hPSC) lines in their research including human embryonic stem cell (hESC) lines and human induced pluirpotency stem (hiPSC) lines. It emphasises the importance of guidance already established for cell culture in general and outlines some further considerations specific to the culture of human pluripotent stem cell lines which may impact on the interpretation of data from radiobiological studies using these cells.

Measuring autoantibodies against IL-17F and IL-22 in autoimmune polyendocrine syndrome type I by radioligand binding assay using fusion proteins.

Autoantibodies against interleukin (IL)-17A, IL-17F and IL-22 have recently been described in patients with autoimmune polyendocrine syndrome type I (APS I), and their presence is reported to be highly correlated with chronic mucocutaneous candidiasis (CMC). The aim of this study was to develop a robust high-throughput radioligand binding assays (RLBA) measuring IL-17F and IL-22 antibodies, to compare them with current enzyme-linked immunosorbent assays (ELISA) of IL-17F and IL-22 and, moreover, to correlate the presence of these antibodies with the presence of CMC. Interleukins are small molecules, which makes them difficult to express in vitro.

Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP).

Rhesus rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi sarcoma-associated herpesvirus. Both these viruses encode complement inhibitors as follows: Kaposi sarcoma-associated herpesvirus-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as a complement inhibitor.

Measurement of cytokines by bioassays: theory and application.

A large number of cytokines have been characterized, of which several have proved successful in the clinic as biotherapeutic agents for malignant, infectious or autoimmune diseases. As biologically active proteins, they cannot be fully characterized by physicochemical methods alone. Thus, biological assays (bioassays) have become increasingly important for their biological characterization and potency determinations.

Biological standardization of human interferon beta: establishment of a replacement world health organization international biological standard for human glycosylated interferon beta.

Human interferon beta (IFN-beta) has been developed as a major biotherapeutic agent for the treatment of multiple sclerosis. Since World Health Organization (WHO) international standards (IS) for IFN-beta were established several years prior to the development of clinical grade IFN-beta products, a number of scientific issues with regard to the biological standardisation of natural and recombinant IFN-beta products have emerged. In order to address these issues, an international collaborative study to evaluate WHO IS and candidate international standards (CIS) of IFN-beta was instigated by the National Institute for Biological Standards and Control (NIBSC) in 2000 and was carried out in the succeeding year.

Biological activity of interleukins-28 and -29: comparison with type I interferons.

Despite binding to receptors distinct from those of type I interferons (IFNs), human interleukins-28A, -28B and -29 (IL-28A, IL-28B and IL-29; alternatively named IFN lambda-2 {IFN-lambda2}, IFN-lambda3 and IFN-lambda1, respectively, or collectively, type III IFNs), a small family of three structurally-related cytokines, are, like IFNs, known to induce antiviral activity. To further biologically characterize IL-28A and IL-29, we compared their activities with those of IFNs in a range of human cell lines. We found that they induced antiviral activity in fewer cell lines and more weakly than IFNs; also IL-28A was less active than IL-29.

Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis.

We have screened for spontaneous anticytokine autoantibodies in patients with infections, neoplasms and autoimmune diseases, because of their increasingly reported co-occurrence. We tested for both binding and neutralizing autoantibodies to a range of human cytokines, including interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon-alpha2 (IFN-alpha2), IFN-omega, IFN-beta, IFN-gamma, tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1) and granulocyte-macrophage colony stimulating factor (GM-CSF), in plasmas or sera. With two notable exceptions described below, we found only occasional, mostly low-titre, non-neutralizing antibodies, mainly to GM-CSF; also to IL-10 in pemphigoid.

Biological assays for interferons.

Interferons (IFN) are potent biologically active proteins synthesised and secreted by somatic cells of all mammalian species. They have been well characterised, especially those of human origin, with respect to structure, biological activities, and clinical therapeutic effects. While structural differences are known to exist among the IFN species that constitute the "IFN family" and despite the existence of different receptors for type I and type II IFN, all species have been shown to exert a similar spectrum of in vitro biological activities in responsive cells.

Establishment of new and replacement World Health Organization International Biological Standards for human interferon alpha and omega.

The complexity of the human interferon-alpha (IFN-alpha) family, with its multiple molecular forms and various biological activities, raises a number of scientific issues with regard to the biological standardisation of natural and recombinant IFN-alpha products. To address such issues and to achieve an appropriate biological standardisation of human interferon-alpha (IFN-alpha) preparations, the National Institute for Biological Standards and Control (NIBSC) of the United Kingdom (UK), in association with the Centre for Biologics Evaluation and Research (CBER) of the United States of America (USA), organised an international collaborative study, which was subsequently divided into two parts. Ninety-three participating laboratories from 29 countries worldwide participated in the first part of the study.