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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/6/3287 |
| Summary: | 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). |
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| ISSN: | 1661-6596 1422-0067 |