Tumor vaccines

Vaccination against tumor, either as a prophylactic procedure or as a mode of treatment, has been a distant goal of immunologists for many years. Ideally, the less specific therapies such as chemotherapy would be replaced by an anti-tumor immune response in the host that would be present on a continuing basis. However, progress has been hampered by a lack of understanding of the role of viruses in human tumor development and the molecular nature of tumor-associated antigens. Recent developments using the techniques of molecular biology and monoclonal antibody reagents are beginning to remedy this deficiency so that vaccination has become a real possibility for certain human cancers. The natural fluctuations in growth rates of some human tumors, and the observation that tumors can occasionally remain dormant for years, has led to the idea that the host has an intrinsic ability to control tumor growth, and that this ability is a property of the immune system. Attempts to enhance this putative control are being made by treating the host with defined biological modifiers that stimulate cells involved in immunity in vivo, and by seeking and expanding such cells in vitro before reinfusing them into the host. These attempts to harness the immune system to attack tumor cells that have evaded the host's defenses might be considered optimistic, but they will at least tell us a great deal about tumor cell behavior and the ability of the host to influence it.     

DNA vaccines

Within the last decade bacterial plasmids encoding foreign antigens have revolutionized vaccine design. Although no DNA vaccine has yet been approved for routine human or veterinary use, the potential of this vaccine modality has been demonstrated in experimental animal models. Plasmid DNA vaccination has shown efficacy against viral, bacterial and parasitic infections, modulated the effects of autoimmune and allergic diseases and induced control over cancer progression. With a better understanding of the basic immune mechanisms that govern induction of protective or curative immune responses, plasmid DNA vaccines and their mode of delivery are continuously being optimized. Because of the simplicity and versatility of these vaccines, various routes and modes of delivery are possible to engage the desired immune responses. These may be T or B effector cell responses able to eliminate infectious agents or transformed cells. DNA vaccines may also induce an immunoregulatory/modulatory or immunosuppressive (tolerizing) response that interferes with the differentiation, expansion or effector functions of B and T cells. In this sense a DNA vaccine may be thought of as a 'negative' vaccine. Pre-clinical and initial small-scale clinical trials have shown DNA vaccines in either of these modes to be safe and well tolerated. Although DNA vaccines induce significant immune responses in small animal trials their efficacy in humans has so far been less promising thus necessitating additional optimizations of this novel vaccine approach.     

Leptospirosis vaccines

Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.     

Plant-based vaccines

Plant systems are reviewed with regard to their ability to express and produce subunit vaccines. Examples of different types of expression systems producing a variety of vaccine candidates are illustrated. Many of these subunit vaccines have been purified and shown to elicit an immune response when injected into animal models. This review also includes vaccines that have been administered orally in a non-purified form as a food or feed product. Cases are highlighted which demonstrate that orally delivered plant-based vaccines can elicit immune responses and in some case studies, confer protection. Examples are used to illustrate some of the inherent advantages of a plant-based system, such as cost, ease of scale-up and convenience of delivery. Also, some of the key steps are identified that will be necessary to bring these new vaccines to the market.     

Malaria vaccines

Although the possibility of a live attenuated malaria vaccine has been considered, current malaria vaccine development activities are dominated by attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, was devoted to vaccine development. The oral presentations in this session and the relevant poster presentations are outlined here by Robin Anders and Allan Saul.     

自播散疫苗

自播散疫苗(Self-disseminating vaccines,SDV)是一种携带抗原编码基因的可复制病毒载体,不但能免疫被接种动物,并能在被接种动物体内复制后再感染与被接种动物接触的动物使其被免疫。黏液瘤病毒是第一个被发现的SDV病毒载体,被成功用于预防兔多发黏液瘤病。由于具有独特的性质,巨细胞病毒(Cytomegalovirus,CMV)可能成为理想的研制SDV的载体。动物源性新发传染病(如埃博拉病毒病等)的不断出现正促进SDV的研制。SDV可能成为一种能有效阻断新发传染病病原体从动物向人传播的生物制品。     

Veterinary vaccines

Vaccination of animals for the prevention of infectious diseases has been practised for a number of years with little change in product composition. Recent advances in molecular biology, pathogenesis and immunology have laid the groundwork for the development of a new generation of veterinary vaccines based on pure subunits as well as live vectored bacteria and viruses. Along with novel methods of antigen preparation, the use of new adjuvants and delivery systems will permit targeting of the appropriate immune response as well as offering flexibility in terms of vaccination protocols. These new technologies are also being applied to the development of vaccines to enhance animal productivity and to control reproduction.     

The newer vaccines

Vaccination is a powerful weapon in the control of animal diseases and many highly successful vaccines have been developed, particularly for virus diseases such as rinderpest, foot-and-mouth disease and Newcastle disease. Despite their extraordinary success, however, there are sufficient problems associated with their production and quality control to warrant a re-examination of the methods in current use. Dissection of virus particles into biologically active fragments has shown that their immunizing activity is usually carried on a single protein. With the identification of the genes coding for these individual proteins it is now possible to express these immunogens in both prokaryotic and eukaryotic cells. Moreover, the immunogenic sites of some of these proteins have been identified, synthesized in E. coli cells or by chemical methods and shown to possess immunizing activity. It is too early to put a time-scale on the commercial availability of the new vaccines. However, the potential advantages of such products over conventional vaccines has led to considerable effort in this field of research and progress has been so rapid that new vaccines could be available within the next few years.     

Recombinant subunit vaccines

Research that may lead to the development of recombinant DNA-based vaccines has been conducted on a broad front. This has resulted in an increased understanding of immunological responsiveness to vaccines, the rational engineering of immunogens, and new means of delivering vaccines.     

Tumor idiotype vaccines

In this study, the contribution of idiotype-positive antitumor antibodies (anti-Id) in protective tumor immunity was investigated. We have previously shown that among various anti-Id generated and typed as the internal-image Ab2 of the tumor-associated antibody (TAA) gp52, only 2F10 antibody induces protective immunity. Increase of the 2F10 idiotope in sera of tumor-bearing mice correlated with long-term survival, while in mice with short survival the circulating 2F10 idiotype decreased. 2F10⁺ Ig were purified from sera of tumor-bearing mice with longterm survival and the amount of 2F10⁺ anti-TAA antibodies was determined. Only about 3% of 2F10⁺ antibodies are 2F10⁺ anti-TAA⁺. Hybridomas were generated from a 2F10 high mouse with spontaneous tumor regression. Only 2 out of 52 tumor-specific hybridomas were 2F10⁺. These results suggest that the protective effect induced by 2F10 vaccination may not be directly mediated by 2F10⁺ antibodies but indirectly through the stimulation of a 2F10-specific cellular immune response.Supported in part by a grant from N.I.H. no. CA51434     

Newcastle disease vaccines

Newcastle disease (ND) is a worldwide problem with severe economic implications, affecting chickens, turkeys and other birds. Newcastle disease virus (NDV), a member of the Paramyxoviridae group can cause disease of diverse severity in accordance with environmental factors. NDV strains are classified according to their virulence into three categories. The lentogenic strains are very mild and naturally inhabit healthy flocks. They can be used as live vaccines even for young chicks. Killed vaccines can be produced from the same viruses following inactivation. Mesogenic ND viruses, which cause mild or inapparent respiratory infections, have recently been banned in many countries even for killed vaccine production due to fears of disease emergence. Velogenic strains are the causative agents of the disease and can be used for the purpose of vaccine challenge test. Production and use of Newcastle disease vaccines are discussed in this review.