Engineering a Novel Bivalent Oral Vaccine against Enteric Fever.
Int J Mol Sci
; 22(6)2021 Mar 23.
Article
em En
| MEDLINE
| ID: mdl-33807097
ABSTRACT
Enteric fever is a major global healthcare issue caused largely by Salmonella enterica 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 S. Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two S. Paratyphi A immunogenic elements flagellin Ha and lipopolysaccharide (LPS) O2. We first replaced the native S. Typhi fliC gene encoding flagellin with the highly homologous fliC gene from S. Paratyphi A using Xer-cise technology. Next, we replaced the S. Typhi rfbE gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O2 LPS and prevent its conversion to O9 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 S. Typhi and S. 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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Base de dados:
MEDLINE
Assunto principal:
Salmonella typhi
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Febre Tifoide
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Vacinas Combinadas
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Vacinas contra Salmonella
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Bioengenharia
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article