Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally
Abstract Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile...
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Nature Portfolio
2025-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01071-7 |
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| author | Marcela F. Pasetti Patricia L. Milletich Jessica A. White Jessica Butts Rebecca C. Brady Michelle D. Dickey Cassandra Ballou Nicole Maier Marcelo B. Sztein Shahida Baqar A. Louis Bourgeois David I. Bernstein |
| author_facet | Marcela F. Pasetti Patricia L. Milletich Jessica A. White Jessica Butts Rebecca C. Brady Michelle D. Dickey Cassandra Ballou Nicole Maier Marcelo B. Sztein Shahida Baqar A. Louis Bourgeois David I. Bernstein |
| author_sort | Marcela F. Pasetti |
| collection | DOAJ |
| description | Abstract Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile toxin LTR192G/L211A (dmLT) delivered intradermally (ID) to healthy adults. Subjects received up to three immunizations at three-week intervals. The vaccine was safe, although it induced mild local and some gastrointestinal adverse events, as well as frequent hyperpigmentation at the injection site. High levels of serum IgG and IgA, LT neutralizing antibodies, and IgG and IgA antibodies in lymphocyte supernatant were elicited post-vaccination, most prominently at the largest dose (2.0 μg). Rates of responses were the highest in subjects who received the largest dose (2.0 μg) and multiple immunizations. The ETEC dmLT vaccine was safe and highly immunogenic, inducing long-lasting systemic and mucosal responses when administered by the ID route. Trial registration Clinical Trials NCT02531685. |
| format | Article |
| id | doaj-art-c4aca7e1e2b04ece91ba5e9c5eed26d4 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-c4aca7e1e2b04ece91ba5e9c5eed26d42025-02-02T12:07:35ZengNature Portfolionpj Vaccines2059-01052025-02-0110111310.1038/s41541-025-01071-7Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermallyMarcela F. Pasetti0Patricia L. Milletich1Jessica A. White2Jessica Butts3Rebecca C. Brady4Michelle D. Dickey5Cassandra Ballou6Nicole Maier7Marcelo B. Sztein8Shahida Baqar9A. Louis Bourgeois10David I. Bernstein11Center for Vaccine Development and Global Health and Department of Pediatrics, University of Maryland School of MedicineCenter for Vaccine Development and Global Health and Department of Pediatrics, University of Maryland School of MedicinePATHThe Emmes CompanyCincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of MedicineCincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of MedicineThe Emmes CompanyDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious DiseasesCenter for Vaccine Development and Global Health and Department of Pediatrics, University of Maryland School of MedicineDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious DiseasesPATHCincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of MedicineAbstract Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile toxin LTR192G/L211A (dmLT) delivered intradermally (ID) to healthy adults. Subjects received up to three immunizations at three-week intervals. The vaccine was safe, although it induced mild local and some gastrointestinal adverse events, as well as frequent hyperpigmentation at the injection site. High levels of serum IgG and IgA, LT neutralizing antibodies, and IgG and IgA antibodies in lymphocyte supernatant were elicited post-vaccination, most prominently at the largest dose (2.0 μg). Rates of responses were the highest in subjects who received the largest dose (2.0 μg) and multiple immunizations. The ETEC dmLT vaccine was safe and highly immunogenic, inducing long-lasting systemic and mucosal responses when administered by the ID route. Trial registration Clinical Trials NCT02531685.https://doi.org/10.1038/s41541-025-01071-7 |
| spellingShingle | Marcela F. Pasetti Patricia L. Milletich Jessica A. White Jessica Butts Rebecca C. Brady Michelle D. Dickey Cassandra Ballou Nicole Maier Marcelo B. Sztein Shahida Baqar A. Louis Bourgeois David I. Bernstein Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally npj Vaccines |
| title | Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally |
| title_full | Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally |
| title_fullStr | Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally |
| title_full_unstemmed | Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally |
| title_short | Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally |
| title_sort | safety and immunogenicity in humans of enterotoxigenic escherichia coli double mutant heat labile toxin administered intradermally |
| url | https://doi.org/10.1038/s41541-025-01071-7 |
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