TY - JOUR
T1 - Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins
T2 - CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA
AU - Nandre, Rahul M.
AU - Ruan, Xiaosai
AU - Duan, Qiangde
AU - Sack, David A.
AU - Zhang, Weiping
N1 - Funding Information:
The authors thank Drs. Ann-Mari Svennerholm (University of Gothenburg, Sweden), June Scott (Emory University), Eileen Barry (University of Maryland), and James Fleckenstein (Washington University) for providing ETEC or recombinant E. coli strains, and Walter Reed Army Institute of Research for supplying dmLT adjuvant. Financial support for this study was provided by NIH ( AI109209-02 ) and research funds from Kansas State University .
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/6/30
Y1 - 2016/6/30
N2 - Diarrhea continues to be a leading cause of death in children younger than 5 years in developing countries. Enterotoxigenic Escherichia coli (ETEC) is a leading bacterial cause of children's diarrhea and travelers' diarrhea. ETEC bacteria initiate diarrheal disease by attaching to host receptors at epithelial cells and colonizing in small intestine. Therefore, preventing ETEC attachment has been considered the first line of defense against ETEC diarrhea. However, developing vaccines effectively against ETEC bacterial attachment encounters challenge because ETEC strains produce over 23 immunologically heterogeneous adhesins. In this study, we applied MEFA (multiepitope fusion antigen) approach to integrate epitopes from adhesin tips or adhesive subunits of CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA adhesins and to construct an adhesin tip MEFA peptide. We then examined immunogenicity of this tip MEFA in mouse immunization, and assessed potential application of this tip MEFA for ETEC vaccine development. Data showed that mice intraperitoneally immunized with this adhesin tip MEFA developed IgG antibody responses to all nine ETEC adhesins. Moreover, ETEC and E. coli bacteria expressing these nine adhesins, after incubation with serum of the immunized mice, exhibited significant reduction in attachment to Caco-2 cells. These results indicated that anti-adhesin antibodies induced by this adhesin tip MEFA blocked adherence of the most important ETEC adhesins, suggesting this multivalent tip MEFA may be useful for developing a broadly protective anti-adhesin vaccine against ETEC diarrhea.
AB - Diarrhea continues to be a leading cause of death in children younger than 5 years in developing countries. Enterotoxigenic Escherichia coli (ETEC) is a leading bacterial cause of children's diarrhea and travelers' diarrhea. ETEC bacteria initiate diarrheal disease by attaching to host receptors at epithelial cells and colonizing in small intestine. Therefore, preventing ETEC attachment has been considered the first line of defense against ETEC diarrhea. However, developing vaccines effectively against ETEC bacterial attachment encounters challenge because ETEC strains produce over 23 immunologically heterogeneous adhesins. In this study, we applied MEFA (multiepitope fusion antigen) approach to integrate epitopes from adhesin tips or adhesive subunits of CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA adhesins and to construct an adhesin tip MEFA peptide. We then examined immunogenicity of this tip MEFA in mouse immunization, and assessed potential application of this tip MEFA for ETEC vaccine development. Data showed that mice intraperitoneally immunized with this adhesin tip MEFA developed IgG antibody responses to all nine ETEC adhesins. Moreover, ETEC and E. coli bacteria expressing these nine adhesins, after incubation with serum of the immunized mice, exhibited significant reduction in attachment to Caco-2 cells. These results indicated that anti-adhesin antibodies induced by this adhesin tip MEFA blocked adherence of the most important ETEC adhesins, suggesting this multivalent tip MEFA may be useful for developing a broadly protective anti-adhesin vaccine against ETEC diarrhea.
KW - Adhesin tip
KW - Diarrhea
KW - ETEC (enterotoxigenic Escherichia coli)
KW - MEFA (multiepitope fusion antigen)
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84971616788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971616788&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2016.04.003
DO - 10.1016/j.vaccine.2016.04.003
M3 - Article
C2 - 27228947
AN - SCOPUS:84971616788
SN - 0264-410X
VL - 34
SP - 3620
EP - 3625
JO - Vaccine
JF - Vaccine
IS - 31
ER -