Oral Vaccine Development by Molecular Display Methods Using Microbial Cells
Oral vaccines are easier to administer than injectable vaccines. To induce an adequate immune response using vaccines, antigenic proteins are usually combined with adjuvant materials. This chapter presents methodologies for the design of oral vaccines usi
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Introduction Almost all vaccines for the prevention of infectious diseases are produced by the inactivation of virulent factors or purification of recombinant antigens. They are administrated by injection in clinical situations. To ensure the safety of injected vaccines, a high level of purification is required, and this results in high production costs [1, 2]. Indeed, some purified antigens do not maintain their effect for long periods after vaccine injection. Moreover, conventional vaccines cannot induce the mucosal immune system due to the injection route. To overcome this limitation, we have developed oral vaccines using molecular display technology, with microbial cells as carriers of antigenic proteins and adjuvants (Fig. 1) [3–6].
1.1 Molecular Display Technology
Both gram-positive and gram-negative bacteria have been investigated as hosts for molecular display technology. Ståhl et al. have developed applications for molecular display using Staphylococcus [7], and it may be feasible to use Lactobacillus and Lactococcus to anchor foreign proteins. For example, Bacillus subtilis subsp.
Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_32, © Springer Science+Business Media New York 2016
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Seiji Shibasaki and Mitsuyoshi Ueda
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Fig. 1 Differences between conventional vaccines and oral vaccines developed by molecular display technology. (a) Conventional vaccines require a complicated procedure including purification, removal of endotoxins (ET), and the preparation of an adjuvant. (b) Oral vaccines by molecular display technology do not require such complicated steps. Additionally, microbial cells act as an adjuvant to enhance immune responses
chungkookjang PgsA [8] or Streptococcus pyogenes M6 can be used to display target proteins [9]. Although diverse microorganisms have been used to display foreign proteins, the display of eukaryotic proteins is sometimes difficult in bacterial cells. The yeast Saccharomyces cerevisiae is a useful host cell for genetic engineering because it folds and glycosylates heterologous eukaryotic proteins. S. cerevisiae also has the advantage of highdensity cultivation in inexpensive medium [10, 11]. In addition, it has the potential to display proteins of other eukaryotic taxa and can display several different proteins on the same cell surface. Therefore, molecular display using the yeast cell surface has many potential benefits and practical applications. S. cerevisiae and Lactobacillus species are generally recognized as safe (GRAS) organisms, and engineered cells can be used to prepare oral vaccines without purification, unlike recombinant protein produced in Escherichia coli. In addition to display systems using yeast, the Lactobacillus system has also been well studied [12].
Oral Vaccine Development by Molecular Display Methods Using Microbial Cells
1.2 Platform for Molecular Display Using Yeast
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Cwps, Flo1, and a- and α-agglutin
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