Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it

Impact of Environmental Factors on Bacteriocin Promoter Activity in Gut-Derived Lactobacillus salivarius

peer-reviewedBacteriocin production is regarded as a desirable probiotic trait that aids in colonization and persistence in the gastrointestinal tract (GIT). Strains of Lactobacillus salivarius, a species associated with the GIT, are regarded as promising probiotic candidates and have a number of associated bacteriocins documented to date. These include multiple class IIb bacteriocins (salivaricin T, salivaricin P, and ABP-118) and the class IId bacteriocin bactofencin A, which show activity against medically important pathogens. However, the production of a bacteriocin in laboratory media does not ensure production under stressful environmental conditions, such as those encountered within the GIT. To allow this issue to be addressed, the promoter regions located upstream of the structural genes encoding the L. salivarius bacteriocins mentioned above were fused to a number of reporter proteins (green fluorescent protein [GFP], red fluorescent protein [RFP], and luciferase [Lux]). Of these, only transcriptional fusions to GFP generated signals of sufficient strength to enable the study of promoter activity in L. salivarius. While analysis of the class IIb bacteriocin promoter regions indicated relatively weak GFP expression, assessment of the promoter of the antistaphylococcal bacteriocin bactofencin A revealed a strong promoter that is most active in the absence of the antimicrobial peptide and is positively induced in the presence of mild environmental stresses, including simulated gastric fluid. Taken together, these data provide information on factors that influence bacteriocin production, which will assist in the development of strategies to optimize in vivo and in vitro production of these antimicrobials.This work was funded by a SFI PI award “Obesibiotics” (11/PI/1137) to PD

ΦCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis

peer-reviewedCrAssphages are an extensive and ubiquitous family of tailed bacteriophages, predicted to infect bacteria of the order Bacteroidales. Despite being found in ~50% of individuals and representing up to 90% of human gut viromes, members of this viral family have never been isolated in culture and remain understudied. Here, we report the isolation of a CrAssphage (ΦCrAss001) from human faecal material. This bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming previous in silico predictions of the likely host. DNA sequencing demonstrates that the bacteriophage genome is circular, 102 kb in size, and has unusual structural traits. In addition, electron microscopy confirms that ΦcrAss001 has a podovirus-like morphology. Despite the absence of obvious lysogeny genes, ΦcrAss001 replicates in a way that does not disrupt proliferation of the host bacterium, and is able to maintain itself in continuous host culture during several weeks

Listeriolysin S, a Novel Peptide Haemolysin Associated with a Subset of Lineage I Listeria monocytogenes

peer-reviewedStreptolysin S (SLS) is a bacteriocin-like haemolytic and cytotoxic virulence factor that plays a key role in the virulence of Group A Streptococcus (GAS), the causative agent of pharyngitis, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. Although it has long been thought that SLS and related peptides are produced by GAS and related streptococci only, there is evidence to suggest that a number of the most notorious Gram-positive pathogenic bacteria, including Listeria monocytogenes, Clostridium botulinum and Staphylococcus aureus, produce related peptides. The distribution of the L. monocytogenes cluster is particularly noteworthy in that it is found exclusively among a subset of lineage I strains; i.e., those responsible for the majority of outbreaks of listeriosis. Expression of these genes results in the production of a haemolytic and cytotoxic factor, designated Listeriolysin S, which contributes to virulence of the pathogen as assessed by murine- and human polymorphonuclear neutrophil–based studies. Thus, in the process of establishing the existence of an extended family of SLS-like modified virulence peptides (MVPs), the genetic basis for the enhanced virulence of a proportion of lineage I L. monocytogenes may have been revealed.Work is funded by the Irish Government under the National Development Plan, through a Science Foundation Ireland Investigator award to CH, PR and PC (06/IN.1/B98)

The effect of a commercially available bacteriophage and bacteriocin on Listeria monocytogenes in coleslaw

Changing consumer attitudes show an increased interest in non-chemical antimicrobials in food preservation and safety. This greater interest of consumers in more ‘natural’ or ‘clean-label’ food interventions is complicated by concurrent demands for minimally processed, ready-to-eat (RTE) foods with long shelf lives. Two viable interventions are bacteriophage (phage) and bacteriocins, a number of which have already been approved for use in food safety. Listeriosis is a serious foodborne infection which affects at-risk members of the population. Listeriosis incidence has increased between 2008 and 2015 and has a case fatality rate of up to 20% with antibiotic intervention. Here, we tested an intervention to attempt to control a pathogenic Listeria monocytogenes strain in a food model using two of these alternative antimicrobials. Phage P100 on its own had a significant effect on L. monocytogenes ScottA numbers in coleslaw over a 10-day period at 4 °C (p ≤ 0.001). A combination of P100 and Nisaplin® (a commercial formulation of the lantibiotic bacteriocin, nisin) had a significant effect on the pathogen (p ≤ 0.001). P100 and Nisaplin® in combination were more effective than Nisaplin® alone, but not P100 alone

RNA phage biology in a metagenomic era

The number of novel bacteriophage sequences has expanded significantly as a result of many metagenomic studies of phage populations in diverse environments. Most of these novel sequences bear little or no homology to existing databases (referred to as the “viral dark matter”). Also, these sequences are primarily derived from DNA-encoded bacteriophages (phages) with few RNA phages included. Despite the rapid advancements in high-throughput sequencing, few studies enrich for RNA viruses, i.e., target viral rather than cellular fraction and/or RNA rather than DNA via a reverse transcriptase step, in an attempt to capture the RNA viruses present in a microbial communities. It is timely to compile existing and relevant information about RNA phages to provide an insight into many of their important biological features, which should aid in sequence-based discovery and in their subsequent annotation. Without comprehensive studies, the biological significance of RNA phages has been largely ignored. Future bacteriophage studies should be adapted to ensure they are properly represented in phageomic studies

Complete genome sequence of Escherichia coli phage APC_JM3.2 isolated from a chicken cecum

Avian pathogenic Escherichia coli (APEC) bacteria are a significant challenge to the poultry industry. Bacteriophages (phages) have the potential to control APEC strains, increasing animal welfare and economic productivity. Here, we report the isolation of an E. coli-infecting phage, APC_JM3.2, isolated from the cecum of a broiler chicken in Ireland

Public health strategies to reduce sugar intake in the UK: An exploration of public perceptions using digital spaces

Objective: To explore UK public perceptions of children's sugar consumption, Public Health England's Change4Life Sugar Smart app and the Soft Drinks Industry Levy, using solicited and unsolicited digital data. Methods: Data from three digital spaces were used as follows: (1) an online questionnaire advertised on parenting forums; (2) posts to UK online parenting forums; and (3) English language Tweets from Twitter. Quantitative data were analysed using descriptive statistics and qualitative data using content and inductive thematic analysis. Results: Data were (study 1) 184 questionnaire participants; (study 2) 412 forum posts; and (study 3) 618 Tweets. In study 1, 94.0% (n = 173) agreed that children in the UK consumed too much sugar and this had a negative health effect (98.4%, n = 181). Environments (n = 135, 73.4%), media/advertising (n = 112, 60.9%) and parents (n = 107, 58.2%) were all reported as barriers to changing children's sugar intake. In study 2, more posts were negative towards the Soft Drinks Industry Levy (n = 189, 45.9%) than positive (n = 145, 35.2%), and themes about the inability of the Levy to affect sugar consumption in children and childhood obesity emerged. Other themes related to distrust of the government, food industry and retailers. In study 3, the Sugar Smart app was viewed positively (n = 474, 76.7%) with its function associated solely with identification of sugar content. Conclusions: Participants accepted the necessity of sugar reduction in children, but recognised the complexity of behaviour change. Public health activities were not always perceived as effective strategies for health promotion. There was some distrust in government, public health officials and the food industry. A less simplistic approach to sugar reduction and more credible sources of information may, therefore, be welcomed by the public

The association between nutrition and physical activity knowledge and weight status of primary school educators

The purpose of this study was to investigate primary school educators’ health status, knowledge, perceptions and behaviour regarding nutrition and physical activity.Thus, nutrition and physical activity knowledge, attitudes,  behaviour and risk factors for the development of non-communicable diseases of 155 educators were assessed in a  cross-sectional survey. Height, weight, waist circumference, blood pressure and random glucose levels were  measured. Twenty percent of the sample had normal weight (body mass index (BMI, kg/m²) &lt; 25), 27.7% were  overweight (BMI 25 to < 30) and 52.3% were obese (BMI < 30). Most of the participants were younger than 45  years (54.2%), females 78.1%, resided in urban areas (50.3%), with high blood pressure ( 140/90 mmHg:  50.3%), and were inactive (48.7%) with a high waist circumference (&gt; 82 cm: 57.4%). Educators’ nutrition and  physical activity knowledge was poor. Sixty-nine percent of educators incorrectly believed that eating starchy foods  causes weight gain and only 15% knew that one should eat five or more fruit and/or vegetables per day. Aspects of poor nutritional knowledge, misconceptions regarding actual body weight status, and challenges in changing health behaviours, emerged as issues which need to be addressed among educators. Educators’ high risk for developing chronic non-communicable diseases (NCDs) may impact on educator absenteeism and subsequently on school  functioning. The aspects of poor nutrition and physical activity knowledge along with educators’ high risk for NCD development may be particularly significant not merely in relation to their personal health but also the learners they teach.Keywords: body weight, educators, health, knowledge, non-communicable diseases, nutrition, perceptions, physical activity, primary schools, risk factor