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Host defense against many infectious diseases depends on the ability of the immune system to recognize and neutralize the invading pathogens. Since Jenner pracited vaccination to prevent virus infection for the first time, immunization process has been remained unchanged over two centaries. Most of the immunogens currently avilable are composed of either the inactivated pathogens or liveattenuated pathogens. There are, however, significant disadvantages to both types of vaccines. The methods of inactivation used to kill pathogens often alters the structure of important immunogenic epitopes, thus this type of vaccine is commonly less potent in producing protective immunity than the unalatered pathogen. In addition, the preferred protective vaccine antigens may be a non-structural component of the pathogen, which would be present in very small amounts, if at all, in a killed vaccine. Another was class of vaccines includes attenuated live-pathogens. They induce subclinical infection in the host and, as a result of the limited replication, produce immune responses similar to those normally caused by the virulent pathogen. One important advange in using live-attenuated vaccines is that they can be delived to mucosal surfaces and induce focal immunity. Since the mucosal surface is the primary site of the entry of many pathogens, immunity at the mucosal surfaces will be much more valuable than systemic immunity in controlling the disease process. One major problem with the development of conventional live vaccine is regulating the degree of attenuation achieved through random mutation and selection. Insufficient reduction in virulence could result in the actual production of disease upon vaccination which over-attenuation could result in insufficient replication in the vaccinates, thereby producing weak protective responses. The recent development in recombinant DNA technology has provided the means to dramatically improve the efficacy of vaccination strategies used to ameliorate infectious diseases in human and other animals. Development of a variety of strong heterologous promoter-enhancer-foreign gene expression systems enables the high-level production of relevant vaccine antigens for use in subunit vaccine formulations. The baculovirus, Autographa califormica nuclear polyhedrosis virus, is an extremely useful helper-independent eukaryotic expression vector. A strong polyhedrin promoter accounts for the synthesis of polyhedrin protein as much as 60% of total cellular protein in Spodoptera frugiperda insect cells in late lytic infection. Since the polyhedrin protein is not required for virus replication, polyhedrin-coding sequence can be replaced by foreign gene, resulting in the high level expression of the desired antigen. Genetic engineering also provides a solution to problems of controlling the degree of attenuation for live-vaccines. Gene encording an identified virulence factor can be specifically removed or modified by recombinant DNA techniques, such that the degree of virulence of the attenuated vaccine agent is closely regulated. Another advantage of using genetically engineered pathogens is that the genes encoding relevant immunogens from other pathogens can be incorporated into the live recombinant vector which would permit their expression upon delivery to vaccinates. Since the recombinant vaccine vector is constructed to actively replicate in vivo, the foreign antigen expressed by the vaccine, vehicle should produce a potent immune response. Adenovirus provides a unique advantage for antigen delivery. Adenoviruses are ubiquitous in the human and animal populations and replicate in the mucosal surfaces of the respiratory and intestinal tracts. Since the early region 3 (E3) of the adenovirus genome is non-essential for adenovirus replication, foreign gene can be inserted into the E3 region. Recombinant adenovirus carrying foreign gene in the E3 locus is helperindependent and grows to high titers in culture. Therefore, recombinant adenoviruses containing foreign insertions at the E3 locus are ideal candidates for safe and efficacious live recombinant vaccine vectors by producing excellent mucosal immunity.
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