The development of a hepatitis C virus prophylactic vaccine strategy

The success of directly-acting antivirals (DAA) has revolutionised hepatitis C virus (HCV) treatment, yet a prophylactic HCV vaccine remains an important clinical asset to achieve HCV elimination by 2030. To date, the development of a prophylactic HCV vaccine has been hindered by viral genomic variability. In human trials, a viral vectored genotype (gt)-1b immunogen induced genotype-1b specific T cell responses targeting highly variable dominant epitopes that displayed reduced cross-recognition of epitope variants at the population level. Therefore, a simian adenoviral vectored (ChAd) HCV T cell vaccine encoding conserved sequences across HCV genotypes was developed, containing known T cell epitopes. In this thesis, I show that conserved sequence vaccines (ChAd-gt1/3, -gt1-6) induce broad, high magnitude, and functional T cell responses that target subdominant highly conserved HCV epitopes in mice, that can be increased by encoding the novel genetic adjuvant—truncated shark invariant chain (sIi47-72) at the 5’ end of the transgene. In addition, I demonstrate that conserved HCV epitopes were not targeted by a ChAd-gt-1b prime and an MVA-gt-3a boost vaccination, unlike a ChAd-gt1-6 prime-boost vaccination, highlighting the importance of priming naïve T cells specific for conserved epitopes. Furthermore, I show that a mixed modality HCV vaccination strategy—combining ChAd-gt1-6 and the recombinant E2Δ123HMW protein does not compromise either the T cell or antibody response compared to either vaccine alone. For the prospects of a single viral vector vaccine that encodes both the gt1-6 T cell immunogen and the E2D123 protein sequence (a ‘bivalent’ vaccine), I demonstrate that a monovalent ChAd-E2D123 prime vaccine induces higher antibody titres targeting E2 and CD81-binding epitopes that neutralise HCVpp/cc, when compared to recombinant E2Δ123HMW protein-induced antibody responses. This body of work represents a significant step forward in the development of a universal prophylactic HCV vaccine and the next step is the assessment of HCV bivalent vaccine induced cross-reactive T cells and broadly neutralising antibodies. A universal HCV vaccine that will contribute to the global elimination strategy will need to target multiple HCV genotypes that circulate in a population and conserved epitopes that can resist viral escape. The work described in this thesis is the next step towards the generation of a universal prophylactic HCV vaccine

Unpacking the Millennials: A Cautionary Tale for Teacher Education

This paper is about the millennial generation. Much has been written about the generation: their character; beliefs; motivations; values; and future potentialities. This literature has gained momentum as marketers, employers, and educators seek to understand the generation as they come of age and enter into positions of social responsibility. The purpose of this paper is to examine the claims made about the Millennials, determine who are making these claims and why, and discuss the utility of such claims for teacher educators. This paper argues that teacher educators should be cautious about accepting and adopting popular discourses about the generation as a basis for the designing and developing millennial appropriate educational practices and pedagogy

Digital Generation Pre-Service Teachers as Change Agents: a Paradox

In this paper I examine the assumptions or ‘cultural models’ (Gee, 1992, p. 60) that 70 aspiring Digital Generation pre-service teachers in south-east Queensland have formed about themselves as future teachers. This paper is drawn from a larger study that focused on the cultural models and resulting discourses that these pre-service teachers expressed about the development of their future lives and careers. In this paper, I argue that these pre-service teachers possess conflicting cultural models about both themselves as teaching professionals and as social activists. While they profess to be educational and social change agents they also profess discourses of educational conservatism and social disengagement. This paper contributes to the ongoing debate about how faculties of teacher education can best prepare teaching professionals in and for the new millennium. It highlights the need to consider the impact of a new generation of teaching professionals in relation to the success or failure of any proposed educational reform

Orbits and Masses in the multiple system LHS 1070

We present a study of the orbits of the triple system LHS1070, with the aim to determine individual masses of its components. Sixteen new relative astrometric positions of the three components in the K band were obtained with NACO at the VLT, Omega CASS at the 3.5m telescope on Calar Alto, and other high-spatial-resolution instruments. We combine them with data from the literature and fit orbit models to the dataset. We derive an improved fit for the orbit of LHS1070B and C around each other, and an estimate for the orbit of B and C around A. The orbits are nearly coplanar, with a misalignment angle of less than 10{\deg}. The masses of the three components are M_A = 0.13 - 0.16 Msun, M_B = 0.077+/-0.005 Msun, and M_C = 0.071+/-0.004 Msun. Therefore, LHS1070C is certainly, and LHS1070B probably a brown dwarf. Comparison with theoretical isochrones shows that LHS1070A is either fainter or more massive than expected. One possible explanation would be that it is a binary. However, the close companion reported previously could not be confirmed.Comment: 9 pages, 8 figures, accepted by Astronomy and Astrophysic

Case Studies of Habitable Trojan Planets in the System of HD 23079

We investigate the possibility of habitable Trojan planets in the HD 23079 star-planet system. This system consists of a solar-type star and a Jupiter-type planet, which orbits the star near the outer edge of the stellar habitable zone in an orbit of low eccentricity. We find that in agreement with previous studies Earth-mass habitable Trojan planets are possible in this system, although the success of staying within the zone of habitability is significantly affected by the orbital parameters of the giant planet and by the initial condition of the theoretical Earth-mass planet. In one of our simulations, the Earth-mass planet is captured by the giant planet and thus becomes a habitable moon.Comment: 24 pages, 8 figures, 3 tables; International Journal of Astrobiology (in press

Diversification and use of bioenergy to maintain future grasslands

Grassland agriculture is experiencing a number of threats including declining profitability and loss of area to other land uses including expansion of the built environment as well as from cropland and forestry. The use of grassland as a natural resource either in terms of existing vegetation and land cover or planting of new species for bioenergy and other nonfood applications presents an opportunity, and potential solution, to maintain the broader ecosystem services that perennial grasslands provide as well as to improve the options for grassland farmers and their communities. This paper brings together different grass or grassland‐based studies and considers them as part of a continuum of strategies that, when also combined with improvements in grassland production systems, will improve the overall efficiency of grasslands as an important natural resource and enable a greater area to be managed, replanted or conserved. These diversification options relate to those most likely to be available to farmers and land owners in the marginally economic or uneconomic grasslands of middle to northern Europe and specifically in the UK. Grasslands represent the predominant global land use and so these strategies are likely to be relevant to other areas although the grass species used may vary. The options covered include the use of biomass derived from the management of grasses in the urban and semi urban environment, semi‐natural grassland systems as part of ecosystem management, pasture in addition to livestock production, and the planting and cropping of dedicated energy grasses. The adoption of such approaches would not only increase income from economically marginal grasslands, but would also mitigate greenhouse gas emissions from livestock production and help fund conservation of these valuable grassland ecosystems and landscapes, which is increasingly becoming a challenge

First-year Transition in Teacher Education: The Pod Experience

Research on student retention and transition in higher education has been an ongoing focus since the 1950s and during the past decade research into this area has gathered momentum as institutions of higher education increasingly recognise the economic and social costs of failing to retain and transition future graduates. Measures to improve transition and retention rates have generally focused on developing strategies to engage students in their studies and tertiary discourses by providing institutional, academic and/or social support. In this paper we discuss ‘Pods’ as an effective and innovative approach to transitioning first-year pre-service teacher education students in regional Victoria. This paper argues that students’ sense of connectedness is greatly enhanced through the grouping of students into Pods in order to promote social and academic engagement and a sense of belonging