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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6)
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 ETE...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-02-01
|
| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2019.1649555 |
| _version_ | 1797677376487817216 |
|---|---|
| author | Hyesuk Seo Ti Lu Sachin Mani A. Louis Bourgeois Richard Walker David A. Sack Weiping Zhang |
| author_facet | Hyesuk Seo Ti Lu Sachin Mani A. Louis Bourgeois Richard Walker David A. Sack Weiping Zhang |
| author_sort | Hyesuk Seo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:44:11Z |
| format | Article |
| id | doaj.art-ddf7d0243b6745b9837a1dd79228b52e |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:44:11Z |
| publishDate | 2020-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-ddf7d0243b6745b9837a1dd79228b52e2023-09-22T08:45:32ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2020-02-0116241942510.1080/21645515.2019.16495551649555Adjuvant 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6)Hyesuk Seo0Ti Lu1Sachin Mani2A. Louis Bourgeois3Richard Walker4David A. Sack5Weiping Zhang6Kansas State University College of Veterinary MedicineKansas State University College of Veterinary MedicinePATH, Center for Vaccine Innovation and AccessPATH, Center for Vaccine Innovation and AccessPATH, Center for Vaccine Innovation and AccessJohns Hopkins University Bloomberg School of Public HealthKansas State University College of Veterinary MedicineDouble-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.http://dx.doi.org/10.1080/21645515.2019.1649555dmltadjuvantdose effectcfa/i/ii/iv mefaenterotoxigenic escherichia coli (etec)antibody response |
| spellingShingle | Hyesuk Seo Ti Lu Sachin Mani A. Louis Bourgeois Richard Walker David A. Sack Weiping Zhang 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) Human Vaccines & Immunotherapeutics dmlt adjuvant dose effect cfa/i/ii/iv mefa enterotoxigenic escherichia coli (etec) antibody response |
| title | 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) |
| title_full | 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) |
| title_fullStr | 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) |
| title_full_unstemmed | 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) |
| title_short | 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: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6) |
| title_sort | 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 dose related enhancement of antibody responses to seven etec adhesins cfa i cs1 cs6 |
| topic | dmlt adjuvant dose effect cfa/i/ii/iv mefa enterotoxigenic escherichia coli (etec) antibody response |
| url | http://dx.doi.org/10.1080/21645515.2019.1649555 |
| work_keys_str_mv | AT hyesukseo adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT tilu adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT sachinmani adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT alouisbourgeois adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT richardwalker adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT davidasack adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 AT weipingzhang adjuvanteffectofenterotoxigenicescherichiacolietecdoublemutantheatlabiletoxindmltonsystemicimmunogenicityinducedbythecfaiiiivmefaetecvaccinedoserelatedenhancementofantibodyresponsestosevenetecadhesinscfaics1cs6 |