Emerging influenza strains in the last two decades: A threat of a new pandemic?

In the last 20 years, novel non-seasonal influenza viruses have emerged, most of which have originated from birds. Despite their apparent inability to cause pandemics, with the exception of H1N1 swine influenza virus, these viruses still constitute a constant threat to public health. While general concern has decreased after the peak of the H5N1 virus, in recent years several novel reassorted influenza viruses (e.g., H7N9, H9N2, H10N8) have jumped the host-species barrier and are under surveillance by the scientific community and public health systems. It is still unclear whether these viruses can actually cause pandemics or just isolated episodes. The purpose of this review is to provide an overview of old and novel potential pandemic strains of recent decades

Sea buckthorn bud extract displays activity against cell-cultured Influenza virus

Introduction - Vaccines and antiviral drugs are the most widely used methods of preventing or treating Influenza virus infection. The role of sea buckthorn (SBT) bud dry extract as a natural antiviral drug against Influenza was investigated.Methods - Influenza virus was cultured in the MDCK cell line, with or without SBT bud extract, and virus growth was assessed by HA and TCID50 virus titration in terms of cytopathic effect on cells. Several concentrations of extract were tested, the virus titer being measured on day 4 after infection.Results - After infection, the virus titer in the control sample was calculated to be 2.5 TCID50/ml; treatment with SBT bud extract reduced the virus titer to 2.0 TCID50/ml at 50 µg/ml, while the HA titer was reduced from 1431 (control) to 178. Concentrations lower than 50 µg/ml displayed an inhibitory effect in the HA assay, but not in the TCID50 virus titration; however, observation of the viral cultures confirmed a slowdown of viral growth at all concentrations.Discussion - Natural dietary supplements and phytotherapy are a growing market and offer new opportunities for the treatment of several diseases and disorders. These preliminary experiments are the first to show that SBT bud extract is able to reduce the growth of the Influenza A H1N1 virus in vitro at a concentration of 50 µg/ml. This discovery opens up the possibility of using SBT bud extract as a valid weapon against Influenza and, in addition, as the starting-point for the discovery of new drugs

Uncoupled redox systems in the lumen of the endoplasmic reticulum. Pyridine nucleotides stay reduced in an oxidative environment.

The redox state of the intraluminal pyridine nucleotide pool was investigated in rat liver microsomal vesicles. The vesicles showed cortisone reductase activity in the absence of added reductants, which was dependent on the integrity of the membrane. The intraluminal pyridine nucleotide pool could be oxidized by the addition of cortisone or metyrapone but not of glutathione. On the other hand, intraluminal pyridine nucleotides were slightly reduced by cortisol or glucose 6-phosphate, although glutathione was completely ineffective. Redox state of microsomal protein thiols/disulfides was not altered either by manipulations affecting the redox state of pyridine nucleotides or by the addition of NAD(P)+ or NAD(P)H. The uncoupling of the thiol/disulfide and NAD(P)+/NAD(P)H redox couples was not because of their subcompartmentation, because enzymes responsible for the intraluminal oxidoreduction of pyridine nucleotides were distributed equally in smooth and rough microsomal subfractions. Instead, the phenomenon can be explained by the negligible representation of glutathione reductase in the endoplasmic reticulum lumen. The results demonstrated the separate existence of two redox systems in the endoplasmic reticulum lumen, which explains the contemporary functioning of oxidative folding and of powerful reductive reactions

Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge

We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratrache

Neisseria meningitidis infection: Who, when and where?

Neisseria meningitidis is a Gram-negative β-proteobacterium responsible for an endemic worldwide infection. The epidemiology and serogroup distribution can change very quickly. The incidence of meningitis infection varies from very rare to more than 1000 cases per 100,000 of the population yearly. The carriage of N. meningitidis, which represents an exclusive human commensal, is asymptomatic, but in rare cases bacteria proliferate in the CNS and rapidly lead to the death of the affected subjects. Host genetic factors, such as single nucleotide polymorphisms, can promote meningococcal disease, being able to influence the individual predisposition to the pathology. Although a reduction in meningococcal disease has been observed in Europe, a continuous surveillance is necessary to control any possible outbreaks of new hypervirulent clones into populations that could modify the epidemiology of meningococcal infections and the clinical spectrum of affected subjects

N. meningitidis and TLR polymorphisms: A fascinating immunomodulatory network

N. meningitidis infections represent a global health problem that can lead to the development of serious permanent sequelae. Although the use of antibiotics and prevention via vaccination have reduced the incidence of meningococcal disease, our understanding regarding N. meningitidis pathogenesis is still limited, especially of those mechanisms responsible for IMD and fulminant or deadly septic shock. These severe clinical presentations occur in a limited number of subjects, whereas about 10% of healthy individuals are estimated to carry the bacteria as a commensal. Since TLR activation is involved in the defense against N. meningitidis, several studies have highlighted the association between host TLR SNPs and a higher susceptibility and severity of N. meningitidis infections. Moreover, TLR SNPs induced variations in immunological responses and in their persistence upon vaccination against meningococcal disease. In the absence of mass vaccination programs, the early identification of risk factors for meningococcal disease would be recommended in order to start immunization strategies and antibiotic treatment in those subjects carrying the risk variants. In addition, it could allow us to identify individuals with a higher risk for severe disease and sequelae in order to develop a personalized healthcare of high-risk subjects based on their genomic profile. In this review, we have illustrated important preliminary correlations between TLR variants and meningococcal susceptibility/severity and with vaccine-induced immune responses

Fighting Neisseria meningitidis: past and current vaccination strategies

Introduction: Neisseria meningitidis infections represent a serious health problem that can lead to invasive meningococcal disease (IMD), a life-threatening condition associated with significant morbidity and mortality. IMD could however be preventable via vaccination. During the past five decades, vaccines against N. meningitidis capsular groups A, C, W and Y were introduced into the market. Recently, group B vaccines based on N. meninigitidis recombinant antigens and outer membrane vesicles have been developed and novel vaccine candidates are under evaluation. Areas covered: In this review we discuss the main meningococcal vaccines available, with focus on immunogenicity data, vaccination impact on disease burden and persistence of vaccine-induced immune response. Preliminary results on new vaccine formulations, potentially able to provide multi-group coverage, are also reported. Expert commentary: Continuous surveillance and optimization of national immunization programs are required in order not only to promptly fight future outbreaks but also to identify possible changes in N. meningitidis epidemiology

Post-translational Modifications of the p53 Protein and the Impact in Alzheimer's Disease: A Review of the Literature

6siOur understanding of Alzheimer's disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses. More recently, the p53 protein, well-known as a genome guardian, has gained attention for its potential role in the early evolution of AD. This is due to the central involvement of p53's in the control of oxidative stress and potential involvement in the Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can affect brain processes, thus contributing to AD development. The following review will explore the impact of p53 PTMs on its function and consequential involvement in AD pathogenesis. The greater understanding of the role of p53 in the pathogenesis of AD could result in more targeted therapies benefiting the many patients of this debilitating disease.reservedClark, James S; Kayed, Rakez; Abate, Giulia; Uberti, Daniela; Kinnon, Paul; Piccirella, SimonaClark, James S; Kayed, Rakez; Abate, Giulia; Uberti, Daniela; Kinnon, Paul; Piccirella, Simon

Cell culture-derived influenza vaccines from Vero cells: a new horizon for vaccine production

In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin–Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies