Engineering a Novel Bivalent Oral Vaccine against Enteric Fever
Enteric fever is a major global healthcare issue caused largely by <i>Salmonella enterica</i> serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically enginee...
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| Language: | English |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/6/3287 |
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| author | Annelise Soulier Claudia Prevosto Mary Chol Livija Deban Rocky M. Cranenburgh |
| author_facet | Annelise Soulier Claudia Prevosto Mary Chol Livija Deban Rocky M. Cranenburgh |
| author_sort | Annelise Soulier |
| collection | DOAJ |
| description | Enteric fever is a major global healthcare issue caused largely by <i>Salmonella enterica</i> serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically engineering the attenuated <i>S.</i> Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two <i>S.</i> Paratyphi A immunogenic elements: flagellin H:a and lipopolysaccharide (LPS) O:2. We first replaced the native <i>S.</i> Typhi <i>fliC</i> gene encoding flagellin with the highly homologous <i>fliC</i> gene from <i>S.</i> Paratyphi A using Xer-cise technology. Next, we replaced the <i>S.</i> Typhi <i>rfbE</i> gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O:2 LPS and prevent its conversion to O:9 through tyvelose epimerase activity. The resulting new strain, ZH9PA, incorporated these two genetic changes and exhibited comparable growth kinetics to the parental ZH9 strain. A formulation containing both ZH9 and ZH9PA strains together constitutes a new bivalent vaccine candidate that targets both <i>S.</i> Typhi and <i>S.</i> Paratyphi A antigens to address a major global healthcare gap for enteric fever prophylaxis. This vaccine is now being tested in a Phase I clinical trial (NCT04349553). |
| first_indexed | 2024-03-10T12:57:48Z |
| format | Article |
| id | doaj.art-25e4f4f042664f3284aaf07c65860c6e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:57:48Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-25e4f4f042664f3284aaf07c65860c6e2023-11-21T11:44:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226328710.3390/ijms22063287Engineering a Novel Bivalent Oral Vaccine against Enteric FeverAnnelise Soulier0Claudia Prevosto1Mary Chol2Livija Deban3Rocky M. Cranenburgh4Prokarium Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UKProkarium Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UKProkarium Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UKProkarium Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UKProkarium Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UKEnteric fever is a major global healthcare issue caused largely by <i>Salmonella enterica</i> serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically engineering the attenuated <i>S.</i> Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two <i>S.</i> Paratyphi A immunogenic elements: flagellin H:a and lipopolysaccharide (LPS) O:2. We first replaced the native <i>S.</i> Typhi <i>fliC</i> gene encoding flagellin with the highly homologous <i>fliC</i> gene from <i>S.</i> Paratyphi A using Xer-cise technology. Next, we replaced the <i>S.</i> Typhi <i>rfbE</i> gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O:2 LPS and prevent its conversion to O:9 through tyvelose epimerase activity. The resulting new strain, ZH9PA, incorporated these two genetic changes and exhibited comparable growth kinetics to the parental ZH9 strain. A formulation containing both ZH9 and ZH9PA strains together constitutes a new bivalent vaccine candidate that targets both <i>S.</i> Typhi and <i>S.</i> Paratyphi A antigens to address a major global healthcare gap for enteric fever prophylaxis. This vaccine is now being tested in a Phase I clinical trial (NCT04349553).https://www.mdpi.com/1422-0067/22/6/3287bacteriasalmonellaTyphiParatyphi Aenteric fevervaccine |
| spellingShingle | Annelise Soulier Claudia Prevosto Mary Chol Livija Deban Rocky M. Cranenburgh Engineering a Novel Bivalent Oral Vaccine against Enteric Fever International Journal of Molecular Sciences bacteria salmonella Typhi Paratyphi A enteric fever vaccine |
| title | Engineering a Novel Bivalent Oral Vaccine against Enteric Fever |
| title_full | Engineering a Novel Bivalent Oral Vaccine against Enteric Fever |
| title_fullStr | Engineering a Novel Bivalent Oral Vaccine against Enteric Fever |
| title_full_unstemmed | Engineering a Novel Bivalent Oral Vaccine against Enteric Fever |
| title_short | Engineering a Novel Bivalent Oral Vaccine against Enteric Fever |
| title_sort | engineering a novel bivalent oral vaccine against enteric fever |
| topic | bacteria salmonella Typhi Paratyphi A enteric fever vaccine |
| url | https://www.mdpi.com/1422-0067/22/6/3287 |
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