Advances in veterinary medicine最新文献

Vaccination is the single most successful medical measure against infectious disease. However, the major barrier for achieving the full protective effect or immunization is how to render attenuated, killed, or subunit vaccines as immunogenic as the fully infectious versions of these microbes (Hughes and Babiuk, 1995; Rabinovich et al., 1994). In the case of PrV, infection with wild-type virus induces an immune response superior to vaccination with a live modified vaccine. After primary intranasal infection with wild-type PrV, the replication of a homologous secondary virus challenge is completely inhibited, and the much sought "sterile immunity" is generated (Kimman et al., 1994). In contrast, the immune response of pigs similarly exposed to PrV mutants, which have been attenuated by removal of the thymidine kinase (TK) and the envelope glycoprotein gE gene (McGregor et al., 1985; Zuckermann et al., 1988), is insufficient for preventing the replication of a homologous wild-type virus challenge (Kimman et al., 1994). Furthermore, inactivated PrV vaccines are even less effective at inducing protective immunity than are live modified PrV vaccines (de Leeuw and Van Orischot, 1985; Stellman et al., 1989; Vannier, 1985). The importance of inactivated and subunit vaccines resides in their stability and safety, since no infectious microbe is being introduced into the animal. However, because of the recognized lower effectiveness of inactivated vaccine types, they usually fall in disfavor when a modified live vaccine alternative is available. There is a critical need to develop strategies to enhance the immunogenicity of live, inactivated, and sub-unit vaccines for human and veterinary use (Hughes and Babiuk, 1995; Rabinovich et al., 1994). Although the inoculation of an animal with a virulent microbe is obviously not the desired method to produce sterile immunity, the immune response generated to infection with wild-type PrV clearly demonstrates that this type of immunity is possible. Research directed at devising strategies to increase the immunogenicity of different types of vaccines is necessary. Because of the wealth of information available on PrV immunity (reviewed by Chinsakchai and Molitor, 1994; Nauwynck, 1997), on PrV vaccines (Kimman et al., 1992, 1994; Mettenleiter, 1991; Scherba and Zuckermann, 1996) and increasingly on the porcine immune system (Lunney, 1993; Lunney et al., 1996; Saalmüller, 1995), the swine herpesvirus model is ideal for investigating the development of vaccine formulations with enhanced immunogenicity. Among the strategies currently being examined for the enhancement of the immunogenicity of inactivated and subunit vaccines is the use of recombinant cytokines administered together with antigen (Hughes and Babiuk, 1995; Rabinovich et al., 1994). The ability to regulate the development of an immune response by cytokines such as IL-12 provides the theoretical basis to use these cytokines as adjuvants to immunopotentiat

Several small and large viruses (e.g., adenovirus, poxvirus, and herpesviruses) have been investigated as vaccine vectors. Each viral system has its advantages and disadvantages. One major advantage for viral vector vaccines is their ability to elicit a protective cell-mediated immunity as well as a humoral response to the antigen delivered by the vector. One major problem to using recombinant viruses as vaccines is the pathogenic potential of the parent virus. Therefore, it is important that along with the optimal expression of the foreign genes and ability to provide protection, the pathogenicity of the vector virus must be reduced during genetic manipulation without affecting its multiplication. The requirements to develop a viral vector, for example, swinepox virus, are a cell culture system that will support the growth of the virus, a suitable nonessential region(s) in the virus genome for insertion of foreign DNA so that virus replication is not affected, a foreign gene(s) that encodes for an immunogenic protein of a swine pathogen, strong transcriptional regulatory elements (promoters) necessary for optimal expression of the foreign genes, a procedure for delivering the foreign gene(s) into the nonessential locus, and a convenient method of distinguishing the recombinant viruses from the parent wild-type virus. Using this methodology, recombinant swinepox virus vaccines expressing pseudorabies virus antigens have been developed and shown to provide protection against challenge. These studies and evidence of local infection of the oral tract by swinepox virus indicate its potential as a recombinant vector for providing immunity against various swine pathogens including those that infect the respiratory and gastrointestinal tracts.