Intranasal immunisation with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses.

Mycobacterium tuberculosis (Mtb) remains a global epidemic despite the widespread use of BCG. Consequently, novel vaccines are required to facilitate a reduction in Mtb morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food-grade bacterium Lactococcus lactis that is used to express selected peptides engineered within the Streptococcus pyogenes M1T1 pilus, allowing for peptide amplification, stabilisation, and enhanced immunogenicity. In the present study, the dominant T cell epitope from the Mtb protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of L. lactis. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B cell responses in intranasally vaccinated mice were analysed by ELISA while T cell responses were analysed by flow cytometry. Serum titres of peptide specific IgG and IgA were detected, confirming vaccination produced antibodies against the cognate peptide. Peptide-specific IgA was also detected across several mucosal sites sampled. Peptide-specific CD4+ T cells were detected at levels similar to those of mice immunised with BCG. PilVax immunisation resulted in an unexpected increase in the numbers of CD3+ CD4- CD8- (double negative, DN) T cells in the lungs of vaccinated mice. Analysis of cytokine production following stimulation with the cognate peptide showed the major cytokine producing cells to be CD4+ T cells and DN T cells. This study provides insight into the antibody and peptide specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study

PilVax – a novel peptide delivery platform for the development of mucosal vaccines

Peptide vaccines are an attractive strategy to engineer the induction of highly targeted immune responses and avoid potentially allergenic and/or reactogenic protein regions. However, peptides by themselves are often unstable and poorly immunogenic, necessitating the need for an adjuvant and a specialised delivery system. We have developed a novel peptide delivery platform (PilVax) that allows the presentation of a stabilised and highly amplified peptide as part of the group A streptococcus serotype M1 pilus structure (PilM1) on the surface of the non-pathogenic bacterium Lactococcus lactis. To show proof of concept, we have successfully inserted the model peptide Ova324–339 into 3 different loop regions of the backbone protein Spy0128, which resulted in the assembly of the pilus containing large numbers of peptide on the surface of L. lactis. Intranasal immunisation of mice with L. lactis PilM1-Ova generated measurable Ova-specific systemic and mucosal responses (IgA and IgG). Furthermore, we show that multiple peptides can be inserted into the PilVax platform and that peptides can also be incorporated into structurally similar, but antigenically different pilus structures. PilVax may be useful as a cost-effective platform for the development of peptide vaccines against a variety of important human pathogens

Historical Analysis: Tracking, Problematizing, and Reterritorializing Achievement and the Achievement Gap

For more than a century, state and federal governments and organizations have used different measures to determine if students and groups of students have achieved in a particular subject or grade level. While the construct of achievement is applied irrespective of student differences, this equal application turns out to be anything but equitable. In this chapter, we work to understand the way achievement plays out for Black students by deconstructing how the word achievement works. In doing so, we track the history of education, testing, and curriculum as it has been applied to Black youth and youth of color

The role of valuation and bargaining in optimising transboundary watercourse treaty regimes

In the face of water scarcity, growing water demands, population increase, ecosystem degradation, climate change, and so on transboundary watercourse states inevitably have to make difficult decisions on how finite quantities of water are distributed. Such waters, and their associated ecosystem services, offer multiple benefits. Valuation and bargaining can play a key role in the sharing of these ecosystems services and their associated benefits across sovereign borders. Ecosystem services in transboundary watercourses essentially constitute a portfolio of assets. Whilst challenging, their commodification, which creates property rights, supports trading. Such trading offers a means by which to resolve conflicts over competing uses and allows states to optimise their ‘portfolios’. However, despite this potential, adoption of appropriate treaty frameworks that might facilitate a market-based approach to the discovery and allocation of water-related ecosystem services at the transboundary level remains both a challenge, and a topic worthy of further study. Drawing upon concepts in law and economics, this paper therefore seeks to advance the study of how treaty frameworks might be developed in a way that supports such a market-based approach to ecosystem services and transboundary waters

The societal context of professional practice: Examining the impact of politics and economics on journalistic role performance across 37 countries

The impact of socio-political variables on journalism is an ongoing concern of comparative research on media systems and professional cultures. However, they have rarely been studied systematically across diverse cases, particularly outside Western democracies, and existing studies that compare western and non-western contexts have mainly focused on journalistic role conceptions rather than actual journalistic practice. Using journalistic role performance as a theoretical and methodological framework, this paper overcomes these shortcomings through a content analysis of 148,474 news stories from 365 print, online, TV, and radio outlets in 37 countries. We consider two fundamental system-level variables—liberal democracy and market orientation—testing a series of hypotheses concerning their influence on the interventionist, watchdog, loyal-facilitator, service, infotainment, and civic roles in the news globally. Findings confirm the widely asserted hypothesis that liberal democracy is associated with the performance of public-service oriented roles. Claims that market orientation reinforces critical and civic-oriented journalism show more mixed results and give some support to the argument that there are forms of “market authoritarianism” associated with loyalist journalism. The findings also show that the interventionist and infotainment roles are not significantly associated with the standard measures of political and economic structure, suggesting the need for more research on their varying forms across societies and the kinds of system-level factors that might explain them

Comparing Journalistic Role Performance Across Thematic Beats: A 37-Country Study

Studies suggest that, at the routine level, news beats function as unique “micro-cultures.” Exploring this “particularist” approach in news content, we compare how the interventionist, watchdog, loyal, service, infotainment, and civic roles materialize across 11 thematic news beats and analyze the moderating effect of platforms, ownership, and levels of political freedom on journalistic role performance in hard and soft news. Based on the second wave of the Journalistic Role Performance (JRP) project, this article reports the findings of a content analysis of 148,474 news items from 37 countries. Our results reveal the transversality of interventionism, the strong associations of some topics and roles, and the limited reach of news beat particularism in the face of moderating variables