Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from Salmonella Choleraesuis in Salmonella Typhimurium. A recombinant Asd + plasmid pCZ...
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Veröffentlicht in: | Scientific reports 2017-07, Vol.7 (1), p.7127-13, Article 7127 |
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Sprache: | eng |
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Zusammenfassung: | Non-typhoidal
Salmonella
are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from
Salmonella
Choleraesuis in
Salmonella
Typhimurium. A recombinant Asd
+
plasmid pCZ1 with the cloned
Salmonella
Choleraesuis O-antigen gene cluster was introduced into three constructed
Salmonella
Typhimurium Δ
asd
mutants: SLT11 (Δ
rfbP
), SLT12 (Δ
rmlB
-
rfbP
) and SLT16 (Δ
rfbP
∆
pagL
::TT
araC
P
BAD
rfbP
). Immunoblotting demonstrated that SLT11 (pCZ1) and SLT12 (pCZ1) efficiently expressed the heterologous O-antigen. In the presence of arabinose, SLT16 (pCZ1) expressed both the homologous and heterologous O-antigens, whereas in the absence of arabinose, SLT16 (pCZ1) mainly expressed the heterologous O-antigen. We deleted the
crp
/
cya
genes in SLT12 (pCZ1) and SLT16 (pCZ1) for attenuation purposes, generating the recombinant vaccine strains SLT17 (pCZ1) and SLT18 (pCZ1). Immunization with either SLT17 (pCZ1) or SLT18 (pCZ1) induced specific IgG against the heterologous O-antigen, which mediated significant killing of
Salmonella
Choleraesuis and provided full protection against a lethal homologous challenge in mice. Furthermore, SLT17 (pCZ1) or SLT18 (pCZ1) immunization resulted in 83% or 50% heterologous protection against
Salmonella
Choleraesuis challenge, respectively. Our study demonstrates that heterologous O-antigen expression is a promising strategy for the development of multivalent
Salmonella
vaccines. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-017-07689-5 |