College of Pharmacy, Chung-Ang University, Seoul, South Korea.
Lett Appl Microbiol. 2014 Mar;58(3):285-91. doi: 10.1111/lam.12188. Epub 2013 Nov 19.
Weak antibody responses to protein antigens after oral immunization remain a serious problem. Yeasts have a rigid cell wall and are inherently resistant to harsh conditions, suggesting that recombinant antigens made in yeast could have a greater chance of making contact with the immune cells of the gastrointestinal (GI) tract in intact form. We compared antibody responses to oral immunization with purified recombinant antigen, used in the conventional manner, and responses to whole recombinant yeast producing the antigen intracellularly. Recombinant capsid protein (CP) of red-spotted grouper necrosis virus (RGNNV) was used as model antigen and Saccharomyces cerevisiae as host. The purified CP was obtained from the S. cerevisiae producing the RGNNV CP. Whole recombinant yeast producing RGNNV CP provoked 9-27 times higher anti-RGNNV CP IgG titres than purified RGNNV CP. Moreover, sera from mice immunized with the recombinant yeast had neutralizing activity against RGNNV, while those from mice immunized with purified CP did not. These results show that whole recombinant yeast is a promising platform for antigen delivery by oral immunization.
Provoking sufficient antibody responses by oral immunization has been an enormous challenge because of the harsh conditions of the gastrointestinal (GI) tract. Immunization strategies using purified antigen to make oral vaccines are incapable of commercialization because excessive amount of antigen is required to provoke antibody responses. Therefore, resolving the problems concerning the cost and effectiveness of oral vaccines is a high priority. Our results suggest that recombinant yeast has great potential for inducing antigen-specific immune responses by oral immunization. We believe that oral immunization using recombinant yeast can be a breakthrough technology.
口服免疫后针对蛋白质抗原的弱抗体反应仍然是一个严重的问题。酵母具有刚性细胞壁，固有地耐受恶劣条件，这表明在酵母中制成的重组抗原更有可能以完整的形式与胃肠道 (GI) 道中的免疫细胞接触。我们比较了口服免疫纯化重组抗原（以常规方式使用）和口服免疫产生细胞内抗原的整个重组酵母的抗体反应。使用红鳍东方鲀坏死病毒 (RGNNV) 的重组衣壳蛋白 (CP) 作为模型抗原和酿酒酵母作为宿主。纯化的 CP 是从生产 RGNNV CP 的酿酒酵母中获得的。产生 RGNNV CP 的整个重组酵母引发的抗 RGNNV CP IgG 滴度比纯化的 RGNNV CP 高 9-27 倍。此外，用重组酵母免疫的小鼠血清具有针对 RGNNV 的中和活性，而用纯化 CP 免疫的小鼠血清则没有。这些结果表明，整个重组酵母是通过口服免疫递送抗原的有前途的平台。
由于胃肠道 (GI) 道的恶劣条件，通过口服免疫引发足够的抗体反应一直是一个巨大的挑战。使用纯化抗原制造口服疫苗的免疫策略不能商业化，因为需要大量抗原才能引发抗体反应。因此，解决口服疫苗的成本和有效性问题是当务之急。我们的结果表明，重组酵母在通过口服免疫诱导抗原特异性免疫反应方面具有巨大潜力。我们相信，使用重组酵母进行口服免疫可能是一项突破性技术。
