Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates.

Access control : allocating resources to selfish agents

The ultimate goal of an authorisation system is to allocate each user the level of access they need to complete their job - no more and no less. This proves to be challenging in an organisational setting because on one hand employees need enough access to perform their tasks, while on the other hand more access will bring about an increasing risk of misuse - either intentionally, where an employee uses the access for personal benefit, or unintentionally through carelessness, losing the information or being socially engineered to give access to an adversary. With the goal of developing a more dynamic authorisation model, we have adopted a game theoretic framework to reason about the factors that may affect users’ likelihood to misuse a permission at the time of an access decision. Game theory provides a useful but previously ignored perspective in authorisation theory: the notion of the user as a self-interested player who selects among a range of possible actions depending on their pay-offs.

(Anti)Queer : introduction

The ‘anti- of ‘(Anti)Queer’ is a queer anti. In particle physics, a domain of science which was for a long time peddled as ultimately knowable, rational and objective, the postmodern turn has made everything queer (or chaotic, as the scientific version of this turn is perhaps more commonly named). This is a world where not only do two wrongs not make a right, but a negative and positive do not calmly cancel each other out to leave nothing, as mathematics might suggest. When matter meets with anti-matter, the resulting explosion can produce not only energy - heat and light? - but new matter. We live in a world whose very basics are no longer the electron and the positron, but an ever proliferating number of chaotic, unpredictable - queer? - subatomic particles. Some are ‘charmed’, others merely ‘strange’ . Weird science indeed. The ‘Anti-’ of ‘Anti-queer’ does not place itself neatly into binaries. This is not a refutation of all that queer has been or will be. It is explicitly a confrontation, a challenge, an attempt to take seriously not only the claims made for queer but the potent contradictions and silences which stand proudly when any attempt is made to write a history of the term. Specifically, ‘Anti-Queer’ is not Beyond Queer, the title of Bruce Bawer’s 1996 book which calmly and self-confidently explains the failings of queer, extols a return to a liberal political theory of cultural change and places its own marker on queer as a movement whose purpose has been served. We are not Beyond Queer. And if we are Anti-Queer, it is only to challenge those working in the arena to acknowledge and work with some of the facts of the movement’s history whose productivity has been erased with a gesture which has, proved, bizarrely, to be reductive and homogenising.

Ontology-based specific and exhaustive user profiles for constraint information fusion for multi-agents

Intelligent agents are an advanced technology utilized in Web Intelligence. When searching information from a distributed Web environment, information is retrieved by multi-agents on the client site and fused on the broker site. The current information fusion techniques rely on cooperation of agents to provide statistics. Such techniques are computationally expensive and unrealistic in the real world. In this paper, we introduce a model that uses a world ontology constructed from the Dewey Decimal Classification to acquire user profiles. By search using specific and exhaustive user profiles, information fusion techniques no longer rely on the statistics provided by agents. The model has been successfully evaluated using the large INEX data set simulating the distributed Web environment.

Property Agents and Motor Dealers Act : strike three

The Tourism, Racing and Fair Trading (Miscellaneous Provisions) Act 2002 (“the Act”) which was passed on 18 April 2002 contains a number of significant amendments relevant to the operation of the Property Agents and Motor Dealers Act 2000. The main changes relevant to property transactions are: (i) Changes to the process for appointment of a real estate agent and consolidation of the appointment forms; (ii) Additions to the disclosure obligation of agents and property developers; (iii) Simplification of the process for commencing the cooling off period; (iv) Alteration of the common law position concerning when the parties are bound by a contract; (v) Removal of the requirement for a seller’s signature on the warning statement to be witnessed; (vi) Retrospective amendment of s 170 of the Body Corporate and Community Management Act 1997; (vii) Inclusion of a new power to allow inspectors to enter the place of business of a licensee or a marketeer without consent and without a warrant; and (viii) Inclusion of a new power for inspectors to require documents to be produced by marketeers. The majority of the amendments are effective from the date of assent, 24 April 2002, however, some of the amendments do not commence until a date fixed by proclamation. No proclamation has been made at the time of writing (2 May 2002). Where the amendments have not commenced this will be noted in the article. Before providing clients with advice, practitioners should carefully check proclamation details.

Property Agents and Motor Dealers Act : take two

The Property Agents and Motor Dealers Act 2000 commenced on 1 July 2001. Significant changes have now been made to the Act by the Property Agents and Motor Dealers Amendment Act 2001 (“the amending Act”). The amending Act contains two distinct parts. First, ss 11-19 of the amending Act provide for increased disclosure obligations on real estate agents, property developers and lawyers together with an extension of the 5 business day cooling-off period imposed by the original Act to all residential property (other than contracts formed on a sale by auction). These provisions commenced on 29 October 2001. The remaining provisions of the amending Act provide for increased jurisdiction and powers to the Property Agents and Motor Dealers Tribunal (“the Tribunal”) enabling the Tribunal to deal with claims against marketeers. These provisions commenced on the date of assent, 21 September 2001.

Real estate agents, brochure and misleading or deceptive conduct

The decision of the High Court in Butcher v Lachlan Elder Realty Pty Ltd [2004] HCA 60 involves issues that affect every person who is induced to buy real estate in Australia by statements in sales brochures distributed by real estate agents. One of these issues is the extent to which estate agents unwittingly engage in misleading or deceptive conduct under s 52 of the Trade Practices Act 1974 (Cth) (‘the Act’) when they distribute sales brochures that contain untrue or misleading statements prepared by others. A further issue is the extent to which agents can escape liability by relying on disclaimers about the authenticity of false statements contained in brochures prepared by them.