Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member

Cured by DNA-genetic immunization in the therapeutic sector

Historically, immunization has been designed to prevent the onset of infectious disease, with vaccines acting as prophylactic agents. However, over the course of time immunization has evolved to include a therapeutic objective whereby individuals who have already contracted an infectious or neoplastic disease, and where traditional treatment options are limited, are vaccinated. With diseases such as HIV and tuberculosis the limited success of traditional chemotherapeutic and prophylactic approaches has resulted in the experimental advancement of therapeutic genetic immunization, where the host immune system is to be modulated to improve disease prognosis or ultimately, eradicate the infection. Furthermore, for cancer, a major non-infectious disease, similar experimental treatments are underway. Here we will explore how genetic immunization enables re-direction of the host immune system resulting in the development of effective immune responses

The malaria war

The 25th of April is a national day to honour the members of the Australian and New Zealand Army Corps (ANZAC), who gave their lives at Gallipoli during the First World War (WWI). The 25th of April has also been designated World Malaria Day by the World Health Organization (WHO), and is commemorated every year to bring awareness of deaths caused by malaria infection and global efforts to control infection. There is no coincidence that these two commemorative events are on the same day, as military campaigns suffered great burdens caused by malaria infection during WWI. Malaria infection is yet to be eradicated from human history; fundamental discoveries of malaria and its control were developed during WWI and the fight against malaria continues to this date. This article focuses on the discovery of malaria prior to WWI, the impact that malaria had on military in the war, and the development of control measures taken to minimize these effects and to subsequently eradicate the disease in many countries

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine▿

Attenuated Salmonella strains are currently in production as vaccines for protection of animals against salmonellosis. Such commercial strains offer the potential to deliver heterologous antigen to protect animals against other diseases. One vaccine strain, attenuated Salmonella enterica serovar Typhimurium (STM-1), was tested for the ability to deliver ovalbumin and to induce immune responses in mice. Two vaccine trials were performed testing the influence of promoter choice, the location of the encoding DNA (plasmid or chromosome), and the effect of preexisting homologous or heterologous immunity. The results demonstrated that humoral and T-cell responses were induced from either of two promoters, from either the plasmid or the chromosome, and that preexposure to the empty homologous vector, STM-1, or the heterologous vector, S. enterica serovar Enteritidis, had no detrimental effect on subsequent antigen-specific responses. In the case of homologous preexposure, responses were generally greater, and this was correlated with an increased uptake of Salmonella by macrophages in vitro after opsonization with immune sera

Phenotypic and molecular characterization of Salmonella enterica serovar Sofia an avirulent species in Australian poultry

Salmonella enterica serovar Sofia (S. Sofia) is often isolated from chickens in Australia. However, despite its high frequency of isolation from chicken and chicken meat products, S. Sofia is rarely associated with animal or human salmonellosis, presumably because this serovar is avirulent in nature. The objective of this work was to investigate the phenotypic and molecular properties of S. Sofia in order to assess its pathogenic potential. Our in vivo studies support the observation that this serovar can colonize tissues, but does not cause disease in chickens. This was further confirmed with tissue culture assays, which showed that the ability of S. Sofia to adhere, invade and survive intracellularly is significantly diminished compared with the pathogenic Salmonella enterica serovar Typhimurium (S. Typhimurium) 82/6915. Molecular analysis of Salmonella pathogenicity islands (SPIs) showed that most of the differences observed in SPI1 to SPI5 of S. Sofia could be attributed to minor changes in the sequences, as indicated by a loss or gain of restriction cleavage sites within these regions. Sequence analysis demonstrated that the majority of virulence genes identified were predicted to encode proteins sharing a high identity (75-100 %) with corresponding proteins from S. Typhimurium. However, a number of virulence genes in S. Sofia have accumulated mutations predicted to affect transcription and/or translation. The avirulence of this serovar is probably not the result of a single genetic change but rather of a series of alterations in a large number of virulence-associated genes. The acquisition of any single virulence gene will almost certainly not be sufficient to restore S. Sofia virulence

Anisakis nematodes in fish and shellfish- from infection to allergies

Anisakidosis is a zoonotic parasitosis induced by members of the family Anisakidae. The anisakid genera includes Anisakis, Pseudoterranova, Hysterothylacium and Contracaecum. The final definitive hosts of these nematodes are marine mammals with a complex life cycle. These nematode parasites use different crustaceans and fish species as intermediate or paratenic hosts and humans are accidental hosts. Human anisakiasis, the infections caused by members of the genus Anisakis, occurs, when seafoods, particularly fish, contaminated with the infective stage (third stage larvae [L3]) of this parasite, are consumed. Pseudoterranovosis, on the other hand is induced by members of the genus Pseudoterranova. These two genera of anisakids have been implicated in human disease globally. There is a rise in reports of gastro-intestinal infections accompanied by allergic reactions caused by Anisakis simplex and Anisakis pegreffii. This review provides an update on current knowledge on Anisakis as a food-borne parasite with special focus on the increasingly reported diversity of fish and crustacean hosts, allergens and immunological cross-reactivity with invertebrate proteins rendering this parasite a significant public health issue

DNA vaccines: a modern-day vaccine revolution

DNA vaccination, or genetic immunisation, has progressed from initial observations 20 years ago through to commercial reality today. Along the way, there have been some stunning successes, including the first experimental vaccination of American condors, to protect them from devastation by the West Nile virus, through to the commercialization of the West Nile viral vaccine for use in horses. Along the way, a large number of research publications have detailed the uses of DNA vaccination as an attempted prophylactic and therapeutic strategy. This chapter will review the short history of DNA vaccination, the underlying immunology and technology, and some of the current and future applications of this revolutionary vaccination technique

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA) are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined