Adjuvants for anti-parasite vaccines

To date the most successful human vaccines use attenuated living pathogens, but the advent of techniques in genetic engineering has meant that pure antigen can be provided in quantity. This has allowed the development of combined vaccines that use only the parasite antigens that convey protective immunity. However, isolated antigens lose immunogenicity so to regain potency, living attenuated carriers like Vaccinia or Salmonella can be used. To avoid the attendant drawbacks of carriers as immunopotentiating agents, adjuvants are under investigation as alternatives for use in vaccines against parasitic infections. In this review, Robert Bomford describes the adjuvants currently being examined for use in vaccines for both protozoan and helminth infections including Leishmania, malaria and Schistosoma. He also points out the drawbacks of using adjuvants and the dilemma of needing to stimulate cell'-mediated immunity while avoiding the immunopathological consequences of doing so.     

Microparticle-based technologies for vaccines

Microparticles have been effectively used for many years as delivery systems for drugs and therapeutic proteins. Their application to the delivery of vaccines is not as extensive, but is growing. Utility has been demonstrated for the delivery of various types of vaccines (e.g., recombinant proteins, plasmid DNA, and peptides) and other vaccine components (e.g., immune potentiators). With respect to delivery of immune potentiators, synergistic effects are often observed whereby much more potent immune responses are induced with a combination than with either component alone. Hence, the prospects for broad application of microparticle-based delivery systems for vaccines are excellent.     

Live recombinant vaccines for humans

Vaccines are clearly the most effective means of preventing infectious diseases and have been particularly successful in controlling viral infection. For example, global small-pox eradication has been the greatest achievement in this regard. However, many existing vaccines are not efficient and there are many diseases against which vaccines are not available at all.     

Liposomes for drugs and vaccines

Application of drugs in therapeutic and preventive medicine is marred by indiscriminate drug action and inability of drugs to reach areas in need of treatment. On the other hand, development of new, more selective drugs is very expensive, lengthy and often uncertain. Recently, much attention has been given to an alternative approach, namely the use of drug delivery systems which are expected to optimize the action of drugs already in existence. One of the more promising systems is liposomes, microscopic spheres made of natural materials (lipids) and able to accommodate large amounts of drug. Fifteen years of liposome research have produced a great deal of knowledge of how the carrier interacts with the biological milieu. In turn, such knowledge has helped us to optimize liposomal drug action in situations as diverse as cancer and microbial therapy, vaccines, oral therapy and medical diagnostics. Some of these applications, especially those involving the phagocytic cells (e.g. antimicrobial therapy and vaccines) seem realistic enough to warrant extensive support from industry.     

Prospects for new viral vaccines

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.     

Recombinant viral vaccines for cancer

Cancer arises from 'self' in a series of steps that are all subject to immunoediting. Therefore, therapeutic cancer vaccines must stimulate an immune response against tumour antigens that have already evaded the body's immune defences. Vaccines presenting a tumour antigen in the context of obvious danger signals seem more likely to stimulate a response. This approach can be facilitated by genetic engineering using recombinant viral vectors expressing tumour antigens, cytokines, or both, from an immunogenic virus particle. We overview clinical attempts to use these agents for systemic immunisation and contrast the results with strategies employing direct intratumoural administration. We focus on the challenge of producing an effective response within the immune-suppressive tumour microenvironment, and discuss how the technology can overcome these obstacles.     

DNA vaccines for allergy treatment

In the past 10 years, a great number of studies have demonstrated that injection of plasmid DNA coding for certain genes results in the induction of humoral and cellular immune responses against the respective gene product. This vaccination approach covers a broad range of possible applications, including the induction of protective immunity against viral, bacterial, and parasitic infections, and it opens new perspectives for treatment of cancer. Surprisingly, DNA immunization also turned out as a promising novel type of immunotherapy against allergy. In this paper, we describe the construction of DNA vaccines for application in allergy models. Beyond, we offer a palette of recently developed modulations to optimize DNA vaccines for allergy treatment by increasing their immunogenicity and minimizing their anaphylactic potential.     

Risk analysis for plant-made vaccines

The production of vaccines in transgenic plants was first proposed in 1990 however no product has yet reached commercialization. There are several risks during the production and delivery stages of this technology, with potential impact on the environment and on human health. Risks to the environment include gene transfer and exposure to antigens or selectable marker proteins. Risks to human health include oral tolerance, allergenicity, inconsistent dosage, worker exposure and unintended exposure to antigens or selectable marker proteins in the food chain. These risks are controllable through appropriate regulatory measures at all stages of production and distribution of a potential plant-made vaccine. Successful use of this technology is highly dependant on stewardship and active risk management by the developers of this technology, and through quality standards for production, which will be set by regulatory agencies. Regulatory agencies can also negatively affect the future viability of this technology by requiring that all risks must be controlled, or by applying conventional regulations which are overly cumbersome for a plant production and oral delivery system. The value of new or replacement vaccines produced in plant cells and delivered orally must be considered alongside the probability and severity of potential risks in their production and use, and the cost of not deploying this technology – the risk of continuing with the status quo alternative.     

Recombinant vaccines for hepatitis E

Hepatitis E virus causes epidemics of acute hepatitis in many developing countries. It infrequently causes disease in developed countries, but avirulent strains might circulate. Some evidence suggests that hepatitis E might be a zoonosis. There is probably only a single serotype. A candidate vaccine consisting of baculovirus-expressed recombinant capsid protein protected macaques from hepatitis E--it passed phase I clinical trials and is currently scheduled for phase II/III clinical trials.     

DNA vaccines for viral diseases

DNA vaccines, with which the antigen is synthesized in vivo after direct introduction of its encoding sequences, offer a unique method of immunization that may overcome many of the deficits of traditional antigen-based vaccines. By virtue of the sustained in vivo antigen synthesis and the comprised stimulatory CpG motifs, plasmid DNA vaccines appear to induce strong and long-lasting humoral (antibodies) and cell-mediated (T-help, other cytokine functions and cytotoxic T cells) immune responses without the risk of infection and without boost. Other advantages over traditional antigen-containing vaccines are their low cost, the relative ease with which they are manufactured, their heat stability, the possibility of obtaining multivalent vaccines and the rapid development of new vaccines in response to new strains of pathogens. The antigen-encoding DNA may be in different forms and formulations, and may be introduced into cells of the body by numerous methods. To date, animal models have shown the possibility of producing effective prophylactic DNA vaccines against numerous viruses as well as other infectious pathogens. The strong cellular responses also open up the possibility of effective therapeutic DNA vaccines to treat chronic viral infections.