|
|
|
| Preparation and Preliminary Evaluation of Triple Oral Vaccine Against Bacterial Diarrhea |
| LIU Di1, YAN Ting1, HE Xiu-juan2, ZHENG Wen-yun2, MA Xing-yuan1 |
1. School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
2. School of Pharmacy, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China |
|
|
|
Abstract Infectious diarrhea disease caused by bacterial pathogens is still one of the most common infectious diseases throughout the world. Due to the emergence of antibiotic resistant bacteria, the treatment effects of antibiotic drugs are not very well. Therefore, it is very important to develop convenient and effective vaccines for the prevention and treatment of bacterial diarrhea. Aimed at enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae and Shigella flexneri, the three major types of pathogenic bacteria, the triple-vaccine based on the heat-labile enterotoxin subunit proteins as antigens and mucosal adjuvants, Vibrio cholerae flagellin protein and Shiga toxin subunit protein as antigens was designed. The corresponding antigens and adjuvant proteins were obtained from engineered Escherichia coli, the alginate-chitosan microspheres were used as oral delivery, and the oral vaccine formulations were prepared. In vitro experiment indicate that the release of protein is very slow in simulated gastric fluid, but prompt and almost complete in simulated intestinal fluid, which suggests that microsphere carrier can achieve the purpose of the intestinal targeted release of vaccine. After immunizing mice, immune indexes were detected, and the results proved that the vaccine stimulated the production of the antigen-specific sIgA and IgG antibody, with significant difference (P<0.05) compared with the control group, and improved the content of CD4+T cells (7.5%~9.5%) and the ratio of CD4+T/CD8+T cells in peripheral blood. As a result, the vaccine induced mucosal and systemic immune responses and could effectively protect the body after immunization.
|
|
Received: 21 April 2017
Published: 25 July 2017
|
|
|
|
|
[1] Sanchez J,Holmgren J. Virulence factors, pathogenesis and vaccine protection in cholera and ETEC diarrhea. Current Opinion in Immunology, 2005, 17(4): 388-398.
[2] Liu L, Johnson H L, Cousens S, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet, 2012, 379(9832): 2151-2161.
[3] Zaidi D,Wine E. An update on travelers’ diarrhea. Curr Opin Gastroenterol, 2015, 31(1): 7-13.
[4] Das J K, Tripathi A, Ali A, et al. Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus. BMC Public Health, 2013, 13(Suppl 3): S11.
[5] Wenneras C,Erling V. Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world. J Health Popul Nutr, 2004, 22(4): 370-382.
[6] Svennerholm A M,Steele D. Microbial-gut interactions in health and disease. Progress in enteric vaccine development. Best Pract Res Clin Gastroenterol, 2004, 18(2): 421-445.
[7] Peirano G, Souza F S,Rodrigues D P. Frequency of serovars and antimicrobial resistance in Shigella spp. from Brazil. Memorias do Instituto Oswaldo Cruz, 2006, 101(3): 245-250.
[8] Das J K, Ali A, Salam R A, et al. Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children. BMC Public Health, 2013, 13(Suppl 3): S10.
[9] Ogra P L, Faden H,Welliver R C. Vaccination strategies for mucosal immune responses. Clinical Microbiology Reviews, 2001, 14(2): 430-445.
[10] Hoebe K, Janssen E,Beutler B. The interface between innate and adaptive immunity. Nature Immunology, 2004, 5(10): 971-974.
[11] da Hora V P, Conceicao F R, Dellagostin O A, et al. Non-toxic derivatives of LT as potent adjuvants. Vaccine, 2011, 29(8): 1538-1544.
[12] Rappuoli R, Pizza M, Douce G, et al. Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunology Today, 1999, 20(11): 493-500.
[13] Melton-Celsa A R. Shiga toxin (Stx) classification, structure, and function. Microbiol Spectr, 2014, 2(4): Ehec-0024-2013.
[14] Klose K E,Mekalanos J J. Differential regulation of multiple flagellins in Vibrio cholerae. Journal of Bacteriology, 1998, 180(2): 303-316. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
