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Rearch On Edible Transgenic Potato Vaccine Of Human Rotavirus

Posted on:2004-02-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:J T LiFull Text:PDF
GTID:1104360095461231Subject:Immunology
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Human Rotaviruses (HRV) are the common cause of severe diarrhea in young children and are estimated to cause nearly one million deaths worldwide annually (Avendano et al., 1993). RV are responsible for 6% of deaths among children under 5 years of age and for 25% of deaths due to diarrheal disease in developing countries. In developed countries, where HRV-acute gastroenteritis are usually mild (Glass et al., 1996), they still cause enormous socioeconomic costs (Berner et al.1999; Johansen et al., 1999). Thus it is urgently needed for developing rotavirus vaccine. Several rotavirus vaccine candidates have been evaluated in clinical trials with various degrees of success. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. But it was withdrawn in less than 1 year after being associated with intussusception, a rare form of bowel blockage found most frequently in young children (Coste et al., 2000). These data suggested that safety is the most above all that should be considered while developing HRV vaccine. In recent years, experiments demonstrated that different vector expressing HRV glycoprotein VP7 was capable of stimulating protective immunity and plays a key role in protection (Andrew et al.,1992; Hoshino et al., 1985; Wang et al. 1999). Previous studies in naturally infected children have shown that intestinal antibodies especially IgA are pivotal in protection from rotavirus reinfection (Giammarioli et al., 1996). As all we know oral immunization is a efficiency method to induce high levels of mucosal IgA injection or mainline (Choi et al., 1998). Thus HRV vaccine may focus on edible vaccine. Subunit vaccines consist of specific macromolecules that induce a protective immune response against a pathogen. These vaccines are the consequence of advances in molecular biology enabling the location of antigens capable of invoking a protective immune response (vaccinogen), the isolation of the corresponding gene(s), and the production of the vaccinogen in an expression system. Subunit technology has improved existing vaccines and has circumvented some limitations of traditional vaccine production. The specific composition of subunit vaccines increases vaccine safety by circumventing the need to uselive viruses or microbes and has thus made them the preferred approach for vaccine manufacturers. Unfortunately, traditional subunit vaccines are expensive to produce and not heat stable (making them reliant on the expensive, often capricious and destinationlimited series of refrigeration steps, sometimes referred to as the 'cold chain', an route from manufacture to vaccination). This limits their availability and use in the low-funded health care systems of developing countries.The utilization of plants as bioreactors for the production of foreign proteins have been increasingly used to acquire experimental immunogens. They are potentially an inexpensive source of antigens that could be parenterally administered or to be used as edible vaccines. To date, several viral antigens have been produced in transgenic plants, which possessed immunogenicity in animals (Haq et al., 1995; Mason et al., 1992; Tacket et al., 1998). As yet, there is no national data about human rotavirus antigen gene expressed in transgenic plants although there are reports of murine (epitope of NSP4) or bovine (VP6) rotavirus (Matsumura et al., 2002; Yu J et al., 2001). So using the VP7 as the antigen in developing edible transgenic plants RV vaccine is a reasonable worthwhile work and may represent a strategy for the development of safe, effective vaccines against rotavirus- induced diarrhea. We reported here the human rotavirus group A antigen gene VP7 expressed in transgenic potato and its immunogenicity in mice.For the construction of plant expression vector PBI-VP7, the whole VP7 gene was cloned as the following: the group A human rotavirus serotype G1 total RNA was isol...
Keywords/Search Tags:Trangeic plants, Human rotavirus, Edible vaccine, Plant expression vector, Oral immunization, Mucosal immune system, VP7 gene, potato, Agrobacterium tumefaciens LBA4404, PBI121, Mucosal adjuvant, Cholera toxin, Cholera toxin subunit B
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