Advances in veterinary medicine最新文献

The large amount of scientific progress made in the last 5 years has allowed a more rational approach to the design of nematode vaccines to develop. Successful experimental trials have been published using two different approaches, one aiming to boost acquired host immunity through vaccination with natural immunogens, the other affecting parasite viability by targeting parasite molecules crucial for nutrition or survival in the host. The individual or combined action of these two vaccination procedures will need to be evaluated with respect to their potential effects on animal health and productivity in the field. To this effect, more data are required concerning the level and duration of immunity of the vaccine-induced protection using acceptable adjuvant systems. In addition, the age at which vaccination is effective and the effect of vaccination on highly susceptible or temporarily immunosuppressed individuals will need to be considered. In the case of gastrointestinal nematodes, the level of pasture contamination with infective larvae is dependent on the worm burdens in the host animal and, in turn, affects the buildup of natural resistance in the host. An appreciation of these complex interactive factors is best achieved through computer simulation models using the powerful simulation software that has recently become available. Further animal trials will need to be performed to establish the necessary data to incorporate into the models and to adapt the model outcomes to the trial results. These epidemiologic and simulation studies should be pursued in parallel with vaccine development so that a better appreciation is gained of the requirements of a successful commercial vaccine.

Under the light of current scientific knowledge, particularly with the progress of molecular biology and of the definition of assays to be performed, it is possible to know, as accurately as possible, the biological properties of a vaccine. Most requirements of EP monographs and Directive 92/18 are founded on that concept. It is clear that there is a balance between safety and efficacy in the case of a live attenuated viral strain that means the more efficient a strain, the less safe it can be. Nevertheless, the problem is more complex; considerable progress has been done to set up new finished products and particularly with the adjuvants which are used now even in combination with live attenuated AD strains. The efficacy of a vaccine can be greatly enhanced, maintaining good local and general safety. But a debate always occurs when it is necessary to determine the acceptability threshold of a vaccine with regard to its safety and efficacy. The points of view are often very divergent. But, in any case, this threshold depends on the local conditions in the different countries. It is clear that objectives of a vaccination program and the requirements about a vaccine cannot be the same in heavily infected countries with a compulsory vaccination program as in countries or regions with a low prevalence of AD infection or with an absence of any infection. Moreover, it must also be considered that vaccines constitute only one element of a control or eradication program targeted against Aujeszky's disease virus.

There are many lines of evidence that suggest the eventual success of gene therapy as a treatment strategy for hemophilia. Because current treatment protocols using plasma-derived or recombinant proteins are far from ideal, the safe and efficient substitution of the defective gene by a normal copy of the gene, or at least its addition, would be of great benefit to the patient and may even be a potential cure. However, the construction of efficient gene therapy vehicles has proven quite difficult in the past and, so far, there is no system that promises to have all the desired features without any serious disadvantages. In general, either the levels of transgene expression are too low (because of the low titers achieved during the generation of the virus) or shortlived (e.g., because of the specific shut-off of the transferred promoter) as is often seen with retroviruses, or in the case of adenoviral vectors, expression is limited because of a strong immune response of the host. Clearly, much work remains to be done to optimize these promising though still imperfect vector systems. In the case of adenovirus, the development of less immunogenic vectors or in vivo modulation of the host immune system may hold promise for improvements. Reports by Yang et al. (1995) and Kay et al. (1995) are promising steps in the direction of immunomodulation. Both attenuate the immune reaction to the adenoviral vector by simultaneous application of either an interleukin or an immunoglobulin, respectively. When IL-2 was administered, the amounts of IgA were reduced and successful administration of a second dose of virus was possible. When CTLA4-Ig, an immunoglobulin that blocks the second signal during antigen presentation, was administered, a markedly prolonged expression of the transgene resulted. In vivo trials with AAV vectors have been carried out for some diseases (Flotte et al., 1993; Kaplitt et al., 1994) but not for hemophilia. Advances in high-titer AAV vector preparation will make this approach more feasible. The pace continues to quicken in the development of nonviral modes of gene delivery (Perales et al., 1994). Although these results are encouraging for the future of gene therapy as a treatment for genetic diseases, much work remains to be done to make this potential alternative a reality for treatment of hemophilia.