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A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Prostate cancer (PCa) provides different types of approach, both as regards the diagnostic and therapeutic aspects, based on the stage of disease. Nowadays, multi-parametric MRI (mpMRI) plays a pivotal role in primary prostate cancer diagnosis and opens the door to the planning of therapeutic st In this fields, conventional morphological imaging showed limited accuracy for assessment of biochemical recurrent prostate cancer (BRPCa), advanced disease and post-therapy monitoring and evaluations. Nuclear medicine has a metabolic or receptor point of view that is often helpful in situations where morphological analysis is not enough. Radiolabeled choline (11C or 18F), base its use on the exalted neoplastic cell membranes turnover and phosphatidylcholine production increase. Thanks to its features, 68Ga-PSMA PET imaging is affirming in entire PCa diagnostic scenario: from local recurrence and advanced disease to primary tumor localization and lymph nodes disease detection; up to the most future-oriented applications that include radio guided surgery (RGS) and theranostics with 177Lu-PSMA. Having achieved excellent levels of diagnostic accuracy does not stop nuclear medicine research which for these comparison scenarios today also proposes the use of 11C-acetate and 18-Fluciclovine that undermine choline PET/CT and PSMA PET/CT results, in a race for the best possible diagnostic performance. Nuclear medicine is also very active in the study of “bone scenario”, it represent an essential evaluation for correct defining the disease stage. As for diagnostics, also in the therapy’s field we observe the flowering of new solutions, to try to improve both the survival and the quality of life of the patient: 223Ra-dichloride and 177Lu-PSMA are two of the most brilliant examples. Finally, the look towards the future cannot ignore the advent of hybrid systems; from this point of view the diamond shining in the near future undoubtedly seems to be PET/MRI, fixing the maximum anatomical definition with finest metabolic-receptor informations.

The ongoing COVID-19 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against SARS-CoV-2. Under this scenario, the interferon-β 1a (IFN-β 1a) whose antiviral potential is already known, and is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β 1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.

The emergence of new influenza strains causing pandemics represents a serious threat to human health. From 1918, four influenza pandemics occurred, caused by H1N1, H2N2 and H3N2 subtypes. Moreover, in 1997 a novel influenza avian strain belonging to the H5N1 subtype infected humans. Nowadays, even if its transmission is still circumscribed to avian species, the capability of the virus to infect humans directly from avian reservoirs can result in fatalities. Moreover, the risk that this or novel avian strains could adapt to inter-human transmission, the development of resistance to anti-viral drugs and the lack of an effective prevention are all incumbent problems for the world population. In this scenario, the identification of broadly neutralizing monoclonal antibodies (mAbs) directed against conserved regions shared among influenza isolates has raised hopes for the development of monoclonal antibody-based immunotherapy and “universal” anti-influenza vaccines.

Background: The cellular adaptive response directed against herpesviruses is widely described in the scientific literature as a pivotal component of the immune system able to control virus replication. The role of humoral immunity remains unclear and controversial. Aims: Discussing the role of adaptive immunity in herpesvirus infection control, highlighting the potential role of the humoral branch of immunity through the description of human monoclonal antibodies directed against herpesviruses. Sources: PubMed search for relevant publications related to protective immunity against Herpesviridae. Content: This review describes the role of adaptive immunity directed against Herpesviridae, focusing on the human humoral response naturally elicited during their infections. Given the ever-increasing interest in monoclonal antibodies as novel therapeutics, the contribution of humoral immunity in controlling productive infection, during both primary infection and reactivations, is discussed. Implications: Human monoclonal antibodies directed against the different Herpesviridae species may represent novel molecular probes to further characterize the molecular machinery involved in herpesvirus infection; and allow the development of novel therapeutics and effective vaccine strategies. N. Clementi, CMI 2017;▪:1 © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

The global burden of herpes simplex virus (HSV) legitimates the critical need to develop new prevention strategies, such as drugs and vaccines that are able to fight either primary HSV infections or reactivations. Moreover, the ever-growing number of patients receiving transplants increases the number of severe HSV infections that are unresponsive to current therapies. Finally, the high global incidence of genital HSV-2 infection increases the risk of perinatal transmission to newborns, in which disseminated infection or central nervous system (CNS) involvement is frequent, with associated high morbidity and mortality rates. There are several key features shared by novel anti-HSV drugs, from currently available optimized drugs to small molecules able to interfere with various virus replication steps. However, several virological aspects of the disease and associated clinical needs highlight why an ideal anti-HSV drug has yet to be developed. © 2016 Elsevier Ltd. All rights reserved.

JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment.Copyright © 2014 Elsevier B.V. All rights reserved.

Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed byin silicoanalysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.

The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.

""Broadly neutralizing monoclonal antibodies (mAbs) directed against different subtypes of influenza A viruses are novel tools for the potential development of effective anti-influenza prophylactic and therapeutic strategies. In both cases, the main candidates for passive transfer and new vaccine development are represented by protective mAbs directed against influenza hemagglutinin (HA). A large number of mAbs directed against influenza HA has been developed to date. However, even if they can be useful and contribute to develop new vaccinal strategies, only few of them can be a good candidate for human administration. In this review, we will describe the most relevant human mAb directed against influenza HA able to recognize highly divergent influenza isolates and possibly useful for human therapy and prophylaxis."" Broadly neutralizing monoclonal antibodies (mAbs) directed against different subtypes of influenza A viruses are novel tools for the potential development of effective anti-influenza prophylactic and therapeutic strategies. In both cases, the main candidates for passive transfer and new vaccine development are represented by protective mAbs directed against influenza hemagglutinin (HA). A large number of mAbs directed against influenza HA has been developed to date. However, even if they can be useful and contribute to develop new vaccinal strategies, only few of them can be a good candidate for human administration. In this review, we will describe the most relevant human mAb directed against influenza HA able to recognize highly divergent influenza isolates and possibly useful for human therapy and prophylaxis.

Little is know about the toxic effects on soils of the pesticide Carboxin, a systemic fungicide used to control plant diseases caused by Basidiomycetes. Studies on abiotic transformation of carboxin report its rapid oxidation to sulfoxide, that is idrolized to other degradation products. This chemical process is favoured by natural sunlight in water, presence of humic substances and soil, UV light in organic solvent. This research was designed to assess the influence of soils with different texture, but similar pedogenetic features, and the possible activity of Pseudomonas aeruginosa on the toxicity reduction of this fungicide. Toxicity tests were performed on the microcrustacean Thamnocephalus platyurus in presence and absence of soils and the bacterium. The results show that the degradation of carboxin in less toxic by-products is significantly increased also in the dark. The phenomenon is influenced by concentration level of the clay in the soil, that causes a rise in the relative adsorbing surface. As a consequence, the availability of carboxin sulfoxide, the first by-oxidation product, is reduced. The results show that a similar consequence is also partially verified for soils that are relatively poor in clay (MND soil), but the reduction of carboxin sulfoxide is in that case due to the presence of organic and inorganic colloids naturally present in soils. It is also proved that the degradation’s kinetic is faster and more complete when P. aeruginosa is present. In this case, along the twenty days of observation, the biotic degradation of carboxin gives inorganic nitrogen products, such as ammonia and nitrite with a final toxicity level lower than the sole use of soils.

In the last years pharmaceuticals have aroused great interest as environmental pollutants for their toxic effects towards non target organisms. This study wants to give attention not only to the overall ecotoxicity of drugs on non target organisms but also to a further adverse effect of drugs, the endocrine interference. The most representative drugs of the widespread classes in environment were investigated as well as their possible photoderivatives, obtained by solar simulator irradiation in water. The photoproducts were identified by their physical features. Bioassays were performed on rotifers and microcrustaceans to assess acute and chronic toxicity, while SOS Chromotest and Ames test were utilized to detect the genotoxic potential of the investigated compounds. The YES-test and the E-screen assay were performed to detect the capability of these substances to bind the human estrogenic receptor  (hER in comparison with 17-estradiol. The results showed that the parent compounds did not show any acute toxicity at the highest concentration tested (100 mg/L) for all the organisms utilized in the bioassays. Chronic exposure to these compounds caused inhibition of growth population on rotifers and crustaceans. Genotoxic and mutagenic effects were frequently found for photoproducts suggesting that transformation products, as already reported, may show effects higher than the respective parental compound. Out of several tested pharmaceuticals, some were positive to YES-assay and/or E-screen assay; in particular, Furosemide and the fibrates (Bezafibrate, Fenofibrate and Gemfibrozil) gave the maximal estrogenic response. Tamoxifen showed its dual activity as agonist and antagonist of hER.

Diagnostics and therapy in neuroendocrine tumors (NETs) has been heavily influenced by nuclear medicine progresses, both from a diagnostic and therapeutic perspective. The introduction of somatostatin-based peptides, labeled to radionuclides (constituting radiopharmaceuticals), such as the current golden standard 68Ga-DOTA-SSAs (SomatoStatin Analogues), has revolutionized the approach to these neoplasms. Peptides-based drugs in NENs’ management have been introduced with OctreoScan® (111In-DTPA-octreotide) in combination with scintigraphy, but today techniques have deeply evolved, allowing better performance together with higher accuracy and sensitivity, in addition to image quality improvements (also in terms of details and anatomical data), especially thanks to the implementation of hybrid techniques, such as SPECT/CT and PET/CT. 68Ga-based radiotracers are not the only diagnostic option in NENs, because of the existence of several tumors (such as insulinomas or malignant neoplasms) that do not express SSAs’ target molecules, thus the utilization of other radiocompunds is needed, such as 18F-FDG.

Prostate cancer (PCa) is considered a major challenge for the many medical disciplines that deal with it; despite the diagnostic and therapeutic improvement, it remains for male sex the most common neoplasm and one of the major causes of death. Clinical presentation is classically varied and can change in relation to the disease state. The diagnostic suspicion must trigger some evaluations by a team of specialists: both biochemical and clinical. To date, despite the galaxy of new diagnostic technologies available, the first steps are still being conducted on the track that sees a central role of serum PSA levels and digito-rectal exploration (DRE). Currently an increasingly emerging role in this field is occupied by MRI, so much so that we can speak of an MRI-targeted biopsy (MRI-TB); in fact, through various methods of use, we try to improve the quality of the samples in order to have more and more accurate biopsies focused on the disease areas. The possibility of using increasingly specific sequences such as diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE) and MR spectctroscopy (MRS) certainly places it at the center of the diagnostic step of this phase of disease. Also from a therapeutic point of view there have been great steps forward in recent years, for both non-metastatic and metastatic disease. In both the diagnostic and therapeutic fields, alongside conventional radiological and pharmacological techniques, nuclear medicine is in a very useful position. In an increasingly targeted approach and in an increasingly “precise” medicine, radiopharmaceuticals such as Ra-223 dichloride and 177Lu-PSMA represent the new frontiers of prostate cancer treatment.

Diagnostics and therapy in neuroendocrine tumors (NETs) has been heavily influenced by nuclear medicine progresses, both from a diagnostic and therapeutic perspective. The introduction of somatostatin-based peptides, labeled to radionuclides (constituting radiopharmaceuticals), such as the current golden standard 68Ga-DOTA-SSAs (SomatoStatin Analogues), has revolutionized the approach to these neoplasms. That is not all: these radiopharmaceuticals have been employed also into a therapeutic context, realizing the so-called PRRT (peptide receptor radionuclide therapy), allowing NENs to be integrated into a comprehensive theragnostic approach, making advantage of the knowledge based on receptor overexpression of neuroendocrine tumors, in particular SSTRs (somatostatin receptors). PRRT is mainly focused on the utilization of 90Y-and 177Lu-based peptides, but in this case another important factor is needed: the internalization process, a pivotal phenomenon that allows the efficacy of the therapy, thanks to the intracellular collection of radioisotopes: in this way, they are able to damage internal structures of neoplastic cells.

Background and aims Vaccines, to limit SARS-CoV-2 infection, were produced and reliable assays are needed for their evaluation. The WHO produced an International-Standard (WHO-IS) to facilitate the standardization/comparison of serological methods. The WHO-IS, produced in limited amount, was never tested for reproducibility. This study aims at developing a reproducible and accessible working standard (WS) to complement the WHO-IS. Materials and methods Sera from vaccinated individuals were used to produce the WSs. The WHO-IS, the WSs and single serum samples (n = 48) were tested on 6 quantitative serological devices. Neutralization assays were performed for the 48 samples and compared with their antibody titers. Results The WS carry an antibody titer 20-fold higher than the WHO-IS. It was reproducible, showed both good linearity and insignificant intra- and inter-laboratory variability. However, the WSs behave differently from the WHO-IS. Analysis of the 48 samples showed that single correlation factors are not sufficient to harmonize results from different assays. Yet, all the devices predict neutralization activity based on the antibody titer. Conclusions A reproducible and highly concentrated WS, specific for IgG against SARS-CoV-2 Spike-glycoprotein was produced. Such characteristics make it particularly suited for the harmonization of commercially available assays and the consequent evaluation of post-vaccinated individuals.

Severe COVID-19 is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members, denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against SARS-CoV-2. In contrast, compared to subjects with other infectious or non-infectious lung pathologies, IFNs are over-represented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites., An in-depth analysis of interferons in COVID-19 reveals differences in their roles based on anatomical location, viral load, age and disease severity. In the upper respiratory tract, high levels of IFN-III are protective and result in mild disease in spite of higher SARS-CoV-2 viral burden while the lower airways of patients with severe COVID-19 demonstrate elevated IFN-I and III, cell death and a reduction in interferon stimulated genes.