TY - JOUR
T1 - Adjuvant effect of enterotoxigenic Escherichia coli (ETEC) double-mutant heat-labile toxin (dmLT) on systemic immunogenicity induced by the CFA/I/II/IV MEFA ETEC vaccine
T2 - Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6)
AU - Seo, Hyesuk
AU - Lu, Ti
AU - Mani, Sachin
AU - Bourgeois, A. Louis
AU - Walker, Richard
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) and James Fleckenstein (Washington University in St. Louis) for providing ETEC or recombinant E. coli strains. We also thank Dr. Fred Cassels, Nicole Maier, and Allison Clifford from PATH for their editorial reviews of the manuscript. Financial support for this study was provided by NIH grant R01AI121067, PATH, and Kansas State University.
Funding Information:
This work was supported by the National Institutes of Health [R01AI121067], PATH, and Kansas State University. The authors thank Drs. Ann-Mari Svennerholm (University of Gothenburg, Sweden), June Scott (Emory University) and James Fleckenstein (Washington University in St. Louis) for providing ETEC or recombinant E. coli strains. We also thank Dr. Fred Cassels, Nicole Maier, and Allison Clifford from PATH for their editorial reviews of the manuscript. Financial support for this study was provided by NIH grant R01AI121067, PATH, and Kansas State University.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.
AB - Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.
KW - CFA/I/II/IV MEFA
KW - Dmlt
KW - adjuvant
KW - antibody response
KW - dose effect
KW - enterotoxigenic Escherichia coli (ETEC)
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U2 - 10.1080/21645515.2019.1649555
DO - 10.1080/21645515.2019.1649555
M3 - Article
C2 - 31361177
AN - SCOPUS:85070996199
SN - 2164-5515
VL - 16
SP - 419
EP - 425
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 2
ER -