Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2014, Vol. 34 Issue (1): 9-14    DOI: 10.13523/j.cb.20140102
    
Protection Effect of Recombinant Oral Rabies Vaccine for Human Use on Immunity of Mice
ZHAO Hui1, ZHENG Wen-ling2, PENG Yi-fei2, MA Wen-li2
1. College of Nature Resources and Environment, South China Agricultural University, Guangzhou 510640, China;
2. Institute of Gene Engineer, Southern Medical University, Guangzhou 510515, China
Download: HTML   PDF(656KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  Purpose To evaluation of the immune protection effect of a oral rabies vaccine and on the immune program in mice for potential human use delivered by live recombinant Saccharomyces cerevisiae. Methods Two groups of Kunming mice (each containing ten mice) were fed by oral gavage with high density live cells of Saccharomyces cerevisiae (S. cerevisiae) INVSCI. At 8 and 12 hours after being fed, the jejunum and ileum of the mice were collected and extracted, respectively, and then those extracts was cultured for 2~3 days at 30℃ for calculation of the survival rates of yeast cells passed through digestive tract. Then the other two groups were fed with two kinds of recombinant yeast expressing rabies virus glycoprotein (G) in different forms including secretory expression pYes-InG and intracellular expression pYes-G. Blood serum and intestine in mice were isolated at 12 hours of fed time. Antibodies against rabies virus in their sera were analyzed by ELISA and the distribution of G antigen in intestinal slices was measured by immunohistochemistry methods. Results The survival rate reached the greatest value of about 36.11%(n=10) at 8 hours after being fed with empty yeast cells and the survival rate after 12 hours was about 0.59% (n=12). The G antigen and low neutralizing antibody titer were detected in tissue samples from the mice fed with yeast cells of secretory expression pYes-InG. The concentration of neutralizing antibody was maintained constant after oral gavage three to four times. However, no antigen or antibody was found in tissue samples from the mice fed with yeast cells of pYes-G. Conclusions Although the new kind of recombinant S.cerevisiae vaccine secreting G antigen (pYes-InG) was unsuitable for preventing infection of rabies virus and treating those patients exposed to rabies virus due to the slow immune response and low antibody titer, they showed potential application for human use considering their immune effect, immune mechanism of oral vaccine, the low production costs and the occupational safety regulations.

Key wordsRabies vaccine for human use      Drug delivery vector      Oral administration     
Received: 15 October 2013      Published: 25 January 2014
ZTFLH:  Q352  
Cite this article:

ZHAO Hui, ZHENG Wen-ling, PENG Yi-fei, MA Wen-li. Protection Effect of Recombinant Oral Rabies Vaccine for Human Use on Immunity of Mice. China Biotechnology, 2014, 34(1): 9-14.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20140102     OR     https://manu60.magtech.com.cn/biotech/Y2014/V34/I1/9

[1] Kim S H, Lee K Y, Jang Y S. Mucosal immune system and M cell-targeting strategies for oral mucosal vaccination. Immune Netw, 2012, 12(5):165-175.
[2] Mutsch M, Zhou W, Phodes P, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N Engl J Med, 2004, 350(9):896-903.
[3] Czerkinsky C, Holmgren J. Enteric vaccines for the developing world: a challenge for mucosal mmunology. Mucosal Immunol, 2009, 2(4): 284-287.
[4] Mestecky J, Nguyen H, Czerkinsky C, et al. Oral immunization: an update. Curr Opin Gastroenterol, 2008, 24(6): 713-719.
[5] Azizi A, Kumar A, Diaz-Mitoma F, et al. Enhancing oral vaccine potency by targeting intestinal M cells. PloS Pathog, 2010, 6(11): e1001147-7.
[6] Katz D E, DeLorimier A J, Wolf M K, et al. Oral immunization of adult volunteers with microencapsulated enterotoxigenic Escherichia coli (ETEC) CS6 antigen. Vaccine, 2003, 21(5-6): 341-346.
[7] Frey A, Giannasca K T, Weltzin R, et al. Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting. J Exp Med, 1996, 184 (3): 1045-1059.
[8] Tacket C O. Plant-based oral vaccines: results of human trials. Curr Top Mircobiol Immunol, 2009, 332: 103-117.
[9] Pniewski T, Kapusta J, Bociag P, et al. Plant expression, lyophilisation and storage of HBV medium and large surface antigens for a prototype oral vaccine formulation. Plant Cell Rep, 2012, 31(3): 585-595.
[10] Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting Interleukin-10. Science.2000, 289: 1352-1355.
[11] Chatel J M. Pothelune L, Ah-Leung S, et al. In vivo transfer plasmid from food-grade transiting lactococci to murine epithelial cells. Gene Ther, 2008, 15(16):1184-1190.
[12] Bermúdez-Humarán L G, Kharrat P, Chatel J M, et al. Lactococci and lactoacili as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Microbial Cell Factories, 2011, 10(suppl 1): S4.
[13] Liu M A. Immunologic basis of vaccine vectors. Immunity, 2010, 33(4): 504-515.
[14] 赵慧, 郑文岭, 高洋, 等. 狂犬病病毒糖蛋白在酿酒酵母中的表达.微生物学通报, 2009, 36(11): 1705 -1709. Zhao H, Zheng W L, Gao Y, et al. Expression of rabies virus glycoprotein gene in Saccharomyces cerevisiae. Microbiology, 2009, 36(11):1705-1709.
[15] 孙敬方主编. 动物实验方法学. 北京:人民卫生出版社, 2002:47-48. SUN J F. Animal Experiment Methodology.Beijing:Peoples Health Publishing House, 2002:47-48.
[16] Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting Interleukin-10. Science, 2000, 289(5483): 1352-1355.
[17] Drouault S, Corthier G, Ehrlich SD, et al. Survival, physiology, and lysis of Lactococcus lactis in the digestive tract. Appl Environ Microbiol, 1999, 65(11): 4881-4886.
[18] Schreuder MP, Deen C, Boersma WJ, et al. Yeast expressing hepatitis B virus surface antigen determinants on its surface: implications for a possible oral vaccine. Vaccine, 1996, 14(5): 383 -388
[19] Blanquet S, Antonelli R, Laforet L, et al. Living recombinant Saccharomyces cerevisiae secreting proteins or peptides as a new drug delivery system in the gut. J Biotechnol, 2004, 110(1):37-49
[20] Müller, G. Oral delivery of protein drugs: driver for personalized medicine? Curr Issues Mol Biol, 2011, 13(1): 13-24.
[21] Kuolee R, Chen W. M cell-targeted delivery of vaccines and therapeutics. Expert Opin Drug Deliv, 2008, 5(6): 693-702.
[1] Xiao-qian PAN,Xiang-yuan XIONG,Yan-chun GONG,Zi-ling LI,Yu-ping LI. Advances in Research of Oral Anticancer Drug Nanocarrier[J]. China Biotechnology, 2018, 38(9): 65-73.