Expression vectors vaccines

Koprowski, H. and Yusibov, V. (2001). The green revolution plants as heterologous expression vectors. Vaccine 19 2735-2741. 

J. Vlak and R. Keus, "Baculovims Expression Vector System for Production of Viral Vacciues," iu A. Mizrahi, ed.. Viral Vaccines, Wiley-Liss, New York, 1990. 

The field of DNA vaccination started when eukaryotic expression vectors were injected into the muscle of laboratory animals [2]. The authors observed protein expression for more than 2 months after injection and noted that no special delivery system was required to obtain this expression. Subsequently, it was demonstrated that antibodies can be induced simply by injecting plasmid DNA into the muscle of mice [3]. Subsequent studies found that the injection of expression plasmids also leads to the induction of a cytotoxic T-cell response. After injection, the DNA enters cells of the vaccinated host and the encoded gene becomes expressed. This eventually leads to the induction of a cellular cytotoxic T-cell, T-helper, and/or humoral (antibody) immune response. 

Not withstanding the possible value of such inactivated viral vaccines, the bulk of products assessed to date are subunit vaccines. Live vector vaccines expressing HIV genes have also been developed and are now coming to the fore (Table 13.12). 

Yeast expression vectors have been among those most commonly used since the beginning of gene technology. Vectors based on baker s yeast, Saccharomyces cerevisiae, have been especially popular for robust expression of many types of recombinant proteins [90]. For instance, the first commercially available recombinant vaccine, the hepatitis B surface antigen vaccine, was produced from an S. cerevisiae vector [91]. Many other recombinant proteins have also been efficiently expressed in yeast including al-Antitrypsin [92], insulin [93], Epstein-Barr virus envelope protein [94], superoxide dismutase [95] and interferon-a [90]. 

Early animal experiments have underlined the potential of vaccinia-based vector vaccines. Vaccinia virus-housing genes from HIV have clearly been found to elicit both humoral and cell-mediated immune responses in monkeys. Similar responses in other animals have been reported when surface polypeptides from a variety of additional pathogens have been expressed in recombinant vaccinia systems (Table 10.16). Human clinical trials are now in progress. 

NT009 Wu, L., L. Jiang, Z. Zhou, et al. Expression of foot-and-mouth disease virus epitopes in tobacco by a tobacco mosaic virus-based vector. Vaccine 2003 21(27-30) 4390-4398. 

Further comparative studies of LI expression were conducted in transgenic plants versus a TMV expression vector. In this case, the cottontail rabbit papillomavirus (CRPV), a close relative of HPV, was used. Rabbits vaccinated with purihed protein were protected against wart development upon challenge with live CRPV despite the fact that VLPs were not detected in this animal model system (Kohl et al., 2006). 

Commercial Uses of Virus Expression Vectors 4.2.5.1 Vaccines and Therapeutic Proteins... 

Several plant viral vectors have been used to successfully produce vaccines and therapeutic proteins in plants. TMV-based expression vectors represent one of the more successful examples and have produced a wide array of therapeutic proteins such as a-trichosanthin, tumor-specific single-chain antibodies, and a number of vaccine antigens (Table 4.1) (Dalsgaard et al., 1997). More recent examples of plant viral expression vectors utilized for vaccine production are provided in detail in Koprowski and Yusibov (2001), Pogue et al. (2002), and Canizares et al. (2005). 

Selected Examples of Vaccines and Therapeutic Proteins Expressed in Plants Using Plant Viral Expression Vectors... 

The calli used to generate cell lines can be transgenic and express the vaccine or therapeutic protein of interest. Transfer of foreign genes into calli takes place by Agrobacterium-va.Q6M.td transformation, particle bombardment, electroporation of protoplasts, or by viral vectors (Fischer... 

Discusses the engineering of plant virus expression vectors for transient expression of vaccine proteins and other therapeutics in plant tissue... 

Tubulekas, I., P. Berglund, M. Fleeton, and P. Liljestrom, Alphavirus expression vectors and their use as recombinant vaccines a minireview. Gene, 1997. 190(1) 191-5. 

The field of DNA vaccines centers on the ability to deliver genetic material, coding, for desired protein antigens in the context of a mammalian expression vector (Donnelly et al., 1997). It was realized that the immunostimulatory properties observed with DNA vaccines, namely the ability to induce a Thl biased or cell mediated immune response, was attributable in part to the presence of CpG motifs within the plasmid DNA (Klinman et al., 1997). In fact, it was demonstrated that the quality of immune activation by DNA vaccines could be influenced by the deliber-ate alteration of CpG content (Krieg et al., 1998). Further, with the identification of neutralizing CpG motifs it became possible to remove any neutralizing influence from the DNA vaccine plasmids. The end result was the optimization of DNA vaccine plasmids, with respect to immune activation (Krieg et al., 1998). 

Roy P (1990), Use of baculovirus expression vectors development of diagnostic reagents, vaccines and morphological counterparts of bluetongue virus, FEMS Microbiol. Immunol. 2 223-234. 

Graham, F.L. and Prevec, L. (1992). Adenovirus-based expression vectors and recombinant vaccines. In Vaccines New Approaches to Immunological Problems. R.W. Ellis, ed. (Boston Butterworth-Heinemann), pp. 363 390. 

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