Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli.
BACKGROUND:Enterotoxigenic Escherichia coli (ETEC) are common causes of diarrheal morbidity and mortality in developing countries for which there is currently no vaccine. Heterogeneity in classical ETEC antigens known as colonization factors (CFs) and poor efficacy of toxoid-based approaches to date...
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ftdoajarticles:oai:doaj.org/article:d599730e23204a93ae14ea23a87ab036 2023-05-15T15:16:45+02:00 Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. Qingwei Luo Firdausi Qadri Rita Kansal David A Rasko Alaullah Sheikh James M Fleckenstein 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003446 https://doaj.org/article/d599730e23204a93ae14ea23a87ab036 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4309559?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003446 https://doaj.org/article/d599730e23204a93ae14ea23a87ab036 PLoS Neglected Tropical Diseases, Vol 9, Iss 1, p e0003446 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003446 2022-12-31T04:37:54Z BACKGROUND:Enterotoxigenic Escherichia coli (ETEC) are common causes of diarrheal morbidity and mortality in developing countries for which there is currently no vaccine. Heterogeneity in classical ETEC antigens known as colonization factors (CFs) and poor efficacy of toxoid-based approaches to date have impeded development of a broadly protective ETEC vaccine, prompting searches for novel molecular targets. METHODOLOGY:Using a variety of molecular methods, we examined a large collection of ETEC isolates for production of two secreted plasmid-encoded pathotype-specific antigens, the EtpA extracellular adhesin, and EatA, a mucin-degrading serine protease; and two chromosomally-encoded molecules, the YghJ metalloprotease and the EaeH adhesin, that are not specific to the ETEC pathovar, but which have been implicated in ETEC pathogenesis. ELISA assays were also performed on control and convalescent sera to characterize the immune response to these antigens. Finally, mice were immunized with recombinant EtpA (rEtpA), and a protease deficient version of the secreted EatA passenger domain (rEatApH134R) to examine the feasibility of combining these molecules in a subunit vaccine approach. PRINCIPAL FINDINGS:EtpA and EatA were secreted by more than half of all ETEC, distributed over diverse phylogenetic lineages belonging to multiple CF groups, and exhibited surprisingly little sequence variation. Both chromosomally-encoded molecules were also identified in a wide variety of ETEC strains and YghJ was secreted by 89% of isolates. Antibodies against both the ETEC pathovar-specific and conserved E. coli antigens were present in significantly higher titers in convalescent samples from subjects with ETEC infection than controls suggesting that each of these antigens is produced and recognized during infection. Finally, co-immunization of mice with rEtpA and rEatApH134R offered significant protection against ETEC infection. CONCLUSIONS:Collectively, these data suggest that novel antigens could significantly complement current ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 1 e0003446 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Qingwei Luo Firdausi Qadri Rita Kansal David A Rasko Alaullah Sheikh James M Fleckenstein Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Enterotoxigenic Escherichia coli (ETEC) are common causes of diarrheal morbidity and mortality in developing countries for which there is currently no vaccine. Heterogeneity in classical ETEC antigens known as colonization factors (CFs) and poor efficacy of toxoid-based approaches to date have impeded development of a broadly protective ETEC vaccine, prompting searches for novel molecular targets. METHODOLOGY:Using a variety of molecular methods, we examined a large collection of ETEC isolates for production of two secreted plasmid-encoded pathotype-specific antigens, the EtpA extracellular adhesin, and EatA, a mucin-degrading serine protease; and two chromosomally-encoded molecules, the YghJ metalloprotease and the EaeH adhesin, that are not specific to the ETEC pathovar, but which have been implicated in ETEC pathogenesis. ELISA assays were also performed on control and convalescent sera to characterize the immune response to these antigens. Finally, mice were immunized with recombinant EtpA (rEtpA), and a protease deficient version of the secreted EatA passenger domain (rEatApH134R) to examine the feasibility of combining these molecules in a subunit vaccine approach. PRINCIPAL FINDINGS:EtpA and EatA were secreted by more than half of all ETEC, distributed over diverse phylogenetic lineages belonging to multiple CF groups, and exhibited surprisingly little sequence variation. Both chromosomally-encoded molecules were also identified in a wide variety of ETEC strains and YghJ was secreted by 89% of isolates. Antibodies against both the ETEC pathovar-specific and conserved E. coli antigens were present in significantly higher titers in convalescent samples from subjects with ETEC infection than controls suggesting that each of these antigens is produced and recognized during infection. Finally, co-immunization of mice with rEtpA and rEatApH134R offered significant protection against ETEC infection. CONCLUSIONS:Collectively, these data suggest that novel antigens could significantly complement current ... |
format |
Article in Journal/Newspaper |
author |
Qingwei Luo Firdausi Qadri Rita Kansal David A Rasko Alaullah Sheikh James M Fleckenstein |
author_facet |
Qingwei Luo Firdausi Qadri Rita Kansal David A Rasko Alaullah Sheikh James M Fleckenstein |
author_sort |
Qingwei Luo |
title |
Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
title_short |
Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
title_full |
Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
title_fullStr |
Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
title_full_unstemmed |
Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. |
title_sort |
conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic escherichia coli. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003446 https://doaj.org/article/d599730e23204a93ae14ea23a87ab036 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 1, p e0003446 (2015) |
op_relation |
http://europepmc.org/articles/PMC4309559?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003446 https://doaj.org/article/d599730e23204a93ae14ea23a87ab036 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003446 |
container_title |
PLOS Neglected Tropical Diseases |
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9 |
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1 |
container_start_page |
e0003446 |
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