The treatment and prevention of parasitism in both humans and livestock continues to rely almost exclusively on the use of antiparasitic drugs – an approach which has limitations, particularly as reinfection, which occurs rapidly in endemic regions, is not prevented. In addition, the widespread appearance of drug-resistant parasites of animals (Kaplan, 2004;) together with emerging evidence of resistance problems in human parasites (Fallon et al. 1995; Ismail et al. 1996; De Clerq et al. 1997; East African Network for Monitoring Antimalarial Treatment, 2003), emphasise the importance of developing alternative methods of control, with anti-parasite vaccines a prime target.

Ectoparasites of livestock are of great economic and social importance but their effective control remains difficult. The feasibility of vaccination as a novel control measure was established over a decade ago with the commercial release of a recombinant vaccine against the cattle tick Boophilus microplus. Since then, research has continued on ticks and other ectoparasites. While some ectoparasite species will undoubtedly be refractory to immunological control, for others there has been a steady accumulation of knowledge of partially protective antigens, now accelerating through the application of genomic technologies. Nevertheless, progress towards usable, commercially available vaccines has been limited by a number of factors. The number of highly effective antigens is still very small. Although some classes of antigen have been investigated in more detail than others, we have no systematic knowledge of what distinguishes an effective antigen. Much hope has been placed on the potential of multi-antigen mixtures to deliver the efficacy required of a successful vaccine but with little experimental evidence. The application of current knowledge across parasite and host species needs to be explored but little has been done. In most cases, the path to commercial delivery is uncertain. Although many constraints and challenges remain, the need for vaccines and our capacity to develop them can only increase.

Recombinant vaccines have been developed which are highly effective in preventing infection with Taenia ovis in sheep, Taenia saginata in cattle, Taenia solium in pigs and Echinococcus granulosus in livestock animals. T. ovis and T. saginata are economically significant parasites and the commercial success or otherwise of vaccines against them will rely on their economic value. E. granulosus and T. solium are zoonotic parasites that cause cystic hydatid disease and neurocysticercosis, respectively, in humans. Vaccines against these parasites have been developed to assist with the control of transmission of the human diseases rather than for prevention of infections in livestock per se. Regions of high prevalence for cystic hydatid disease and neurocysticercosis occur primarily in the developing world. As a consequence, vaccines against them are of little or no commercially interest – they are Orphan Vaccines. Lack of commercial interest in these vaccines has made public sector support for their development necessary well beyond the research phase trough into completion of commercial scale-up and other more commercially-related assessments. Practical use of the vaccines will require commercial-scale production according to international manufacturing standards. Identifying partners and support in this endeavour is now of prime importance in efforts to achieve the potential of these vaccines as new tools for the control of cystic hydatid disease and neurocysticercosis.

Schistosoma japonicum, Fasciola hepatica and F. gigantica are digenetic trematodes and, therefore, possess similar life cycles. While schistosomiasis japonica has for a long time been recognised as a major disease of both humans and animals, infection with fasciolids has only been considered of relevance to animals. However, a number of recent reports indicate that fasciolosis is becoming a serious public health problem, especially in South America, Egypt and Iran (sporadic cases are also on the increase throughout Europe). Vaccines targeted at animals could play an important role in controlling these three diseases in animals and, by blocking transmission of infection, have a concurrent beneficial effect on disease in humans. Approaches towards identifying and producing vaccines against these parasites are similar and are discussed in this reveiw.

This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.

Amoebiasis, infection by the protozoan parasite Entamoeba histolytica, remains a global health problem, despite the availability of effective treatment. While improved sanitation could lead to the eradication of this disease, it is unlikely that this will occur worldwide in the foreseeable future; thus alternative measures must be pursued. One approach is to develop a vaccine to prevent this deadly disease. Clinical studies indicate that mucosal immunity may provide some protection against recurrent intestinal infection with E. histolytica, but there is no clear evidence that protective immunity develops after amoebic liver abscess. Over the past decade, progress in vaccine development has been facilitated by new animal models that allow better testing of potential vaccine candidates and the application of recombinant technology to vaccine design. Oral vaccines and DNA-based vaccines have been successfully tested in animals models for immunogenicity and efficacy. There has been significant progress on a number of fronts, but there are unanswered questions regarding the effectiveness of immune responses in preventing disease in man and, as yet, no testing of any of these vaccines in humans has been performed. In addition, there are strong economic barriers to developing an amoebiasis vaccine and questions about how and where an effective vaccine would be utilized.

Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding of Leishmania pathogenesis and generation of host protective immunity, together with the completed Leishmania genome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation.

Malaria causes much physical and economic hardship in endemic countries with billions of people at risk. A vaccine would clearly benefit these countries, reducing the requirement for hospital care and the economic impact of infection. Successful immunization with irradiated sporozoites and the fact that repeated exposure to malaria induces partial immunity to infection and high levels of protection against the clinical manifestations, suggest that a vaccine is feasible. Numerous candidate antigens have been identified but the vaccine, which has been promised to be ‘just round the corner’ for many years, remains elusive. The factors contributing to this frustratingly slow progress are discussed including gaps in the knowledge of host/parasite biology, methods to induce potent cell-mediated immune responses, the difficulties associated with defining immune correlates of protection and antigen production and delivery. Finally, the use of attenuated organism vaccines is discussed.

The protozoan parasites Eimeria spp. Toxoplasma gondii and Neospora caninum are significant causes of disease in livestock worldwide and T. gondii is also an important human pathogen. Drugs have been used with varying success to help control aspects of these diseases and commercial vaccines are available for all three groups of parasites. However, there are issues with increasing development of resistance to many of the anti-coccidial drugs used to help control avian eimeriosis and public concerns about the use of drugs in food animals. In addition there are no drugs available that can act against the tissue cyst stage of either T. gondii or N. caninum and thus cure animals or people of infection. All three groups of parasites multiply within the cells of their host species and therefore cell mediated immune mechanisms are thought to be an important component of host protective immunity. Successful vaccination strategies for both Eimeria and Toxoplasma have relied on using a live vaccination approach using attenuated parasites which allows correct processing and presentation of antigen to the host immune system to stimulate appropriate cell mediated immune responses. However, live vaccines can have problems with safety, short shelf-life and large-scale production; therefore there is continued interest in devising new vaccines using defined recombinant antigens. The major challenges in devising novel vaccines are to select relevant antigens and then present them to the immune system in an appropriate manner to enable the induction of protective immune responses. With all three groups of parasites, vaccine preparations comprising antigens from the different life cycle stages may also be advantageous. In the case of Eimeria parasites there are also problems with strain-specific immunity therefore a cocktail of antigens from different parasite strains may be required. Improving our knowledge of the different parasite transmission routes, host-parasite relationships, disease pathogenesis and determining the various roles of the host immune response being at times host-protective, parasite protective and in causing immunopathology will help to tailor a vaccination strategy against a particular disease target. This paper discusses current vaccination strategies to help combat infections with Eimeria, Toxoplasma and Neospora and recent research looking towards developing new vaccine targets and approaches.

The tick-borne protozoan parasites Theileria parva and Theileria annulata cause economically important diseases of cattle in tropical and sub-tropical regions. Because of shortcomings in disease control measures based on therapy and tick control, there is a demand for effective vaccines against these diseases. Vaccines using live parasites have been available for over two decades, but despite their undoubted efficacy they have not been used on a large scale. Lack of infrastructure for vaccine production and distribution, as well as concerns about the introduction of vaccine parasite strains into local tick populations have curtailed the use of these vaccines. More recently, research has focused on the development of subunit vaccines. Studies of immune responses to different stages of the parasites have yielded immunological probes that have been used to identify candidate vaccine antigens. Immunisation of cattle with antigens expressed in the sporozoite, schizont or merozoite stages has resulted in varying degrees of protection against challenge. Although the levels of protection achieved have not been sufficient to allow exploitation for vaccination, there are clearly further lines of investigation, relating to both the choice of antigens and the antigen delivery systems employed, that need to be pursued to fully explore the potential of the candidate vaccines. Improved knowledge of the molecular biology and immunology of the parasites gained during the course of these studies has also opened up opportunities to refine and improve the quality of live vaccines.

Although immunisation protocols for a wide variety of parasitic diseases have been developed, it is often questioned why these do not always reach the market. In this review information about the regulations and procedures that apply to licensing the production and marketing of medicinal preparations, especially parasite vaccines, is presented. These general regulations specify issues on product (quality, safety, efficacy and potency) and production (facilities and consistency). Vaccine developers and manufacturers have to comply with these regulations, which may involve years of research and development. Moreover, where the manufacturer claims specific features of the product, these claims have to be corroborated by (experimental) data. A series of principles has been used to develop vaccines against parasite infections varying from the use of (attenuated) live vaccines to killed vaccines and subunit vaccines. The implications of some specific regulatory issues associated with these approaches are discussed.