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| Status |
Public on Jul 25, 2019 |
| Title |
Molecular and immunological interrogation of a live-attenuated enterotoxigenic Escherichia coli vaccine highlights features unique to wild type infection |
| Platform organism |
Escherichia coli |
| Sample organism |
Homo sapiens |
| Experiment type |
Protein profiling by protein array
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| Summary |
Enterotoxigenic Escherichia coli (ETEC) infections are a common cause of diarrheal illness in low- and middle-income countries. The live-attenuated ACE527 vaccine, adjuvanted with double mutant LT (dmLT), affords clear but partial protection against ETEC challenge inhuman volunteers. Comparatively, initial wild-type ETEC challenge completely protects against severe diarrhea on homologous re-challenge...To investigate molecular determinants of protection, vaccine antigen content was compared to wild-type ETEC, and proteome microarrays were used to assess immune responses following vaccination and ETEC challenge... Although molecular interrogation of the vaccine confirmed expression of targeted canonical antigens, relative to wild-type ETEC, vaccine strains were deficient in production of flagellar antigens, immotile, and lacked production of the EtpA adhesin. Similarly, vaccination ± dmLT elicited responses to targeted canonical antigens, but relative to wild-type challenge, vaccine responses to some potentially protective non-canonical antigens including EtpA were diminished or absent...These studies highlight important differences in vaccine and wild-type ETEC antigen content and call attention to distinct immunologic signatures that could inform investigation of correlates of protection, and guide vaccine antigen selection for these pathogens of global importance.
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| Overall design |
A total of 250 ALS samples were analyzed from 36 subjects: 10 placebo, 13 ACE527 vaccinated, and 13 ACE527+dmLT vaccinated. The vaccine was administered at days 0, 28, and 56. Thirty four of the subjects have 7 samples taken at days 0, 7, 28, 35, 56, and 63 with respect to the first vaccination and another sample taken 7 days after challenge. The remaining two subjects are missing one sample day each.
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| Contributor(s) |
Chakraborty S, Randall A, Vickers TJ, Molina D, Harro CD, DeNearing B, Brubaker J, Sack DA, Bourgeois AL, Felgner PL, Liang X, Mani S, Wenzel H, Townsend RR, Gilmore PE, Darsley MJ, Rasko DA, Fleckenstein JM |
| Citation(s) |
31482013 |
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| Submission date |
Jul 24, 2019 |
| Last update date |
Sep 11, 2019 |
| Contact name |
Arlo Zan Randall |
| E-mail(s) |
arandall@antigendiscovery.com
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| Organization name |
Antigen Discovery Inc
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| Street address |
1 Technology Drive, Suite E309
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| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92618 |
| Country |
USA |
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| Platforms (1) |
| GPL26932 |
Antigen Discovery Inc. ETEC Protein Array |
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| Samples (250)
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| Relations |
| BioProject |
PRJNA556424 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134792_Normalized_Matrix.xlsx |
10.7 Mb |
(ftp)(http) |
XLSX |
| GSE134792_Raw_Data_Matrix.xlsx |
5.2 Mb |
(ftp)(http) |
XLSX |
| Processed data included within Sample table |
| Processed data are available on Series record |
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