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Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines.

Abstract：

:The Salmonella rfc gene encodes the O-antigen polymerase. We constructed three strains in which we replaced the native rfc promoter with the arabinose-dependent araC P(BAD) promoter so that rfc expression was dependent on exogenously supplied arabinose provided during in vitro growth. The three mutant strains were designed to synthesize different amounts of Rfc by altering the ribosome-binding sequence and start codon. We examined these strains for a number of in vitro characteristics compared to an isogenic Deltarfc mutant and the wild-type parent strain. One promoter-replacement mutation, DeltaP(rfc174), yielded an optimal profile, exhibiting wild-type characteristics when grown with arabinose, and Deltarfc characteristics when grown without arabinose. In addition, when administered orally, the DeltaP(rfc174) strain was completely attenuated in for virulence in mice. The DeltaP(rfc174) mutation was introduced into attenuated Salmonella vaccine strain chi9241 (DeltapabA DeltapabB DeltaasdA) followed by introduction of an Asd(+) balanced-lethal plasmid to designed for expression of the pneumococcal surface protein PspA. Mice immunized with either chi9241 or its DeltaP(rfc174) derivative expressing pspA were protected against S. pneumoniae challenge.

journal_name

Vaccine

journal_title

Vaccine

authors

Kong Q,Liu Q,Jansen AM,Curtiss R 3rd

doi

10.1016/j.vaccine.2010.06.074

subject

Has Abstract

pub_date

2010-08-23 00:00:00

pages

6094-103

issue

37

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(10)00902-3

journal_volume

28

pub_type

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