Protective immunity elicited by oral immunization of mice with Salmonella enterica serovar typhimurium braun lipoprotein (Lpp) and acetyltransferase (MsbB) mutants

Tatiana E. Erova, Michelle L. Kirtley, Eric C. Fitts, Duraisamy Ponnusamy, Wallace B. Baze, Jourdan A. Andersson, Yingzi Cong, Bethany L. Tiner, Jian Sha, Ashok Chopra

Research output: Contribution to journalArticle

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Abstract

We evaluated the extent of attenuation and immunogenicity of the ΔlppAB and ΔlppAB ΔmsbB mutants of Salmonella enterica serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and triggered robust innate and adaptive immune responses. Comparable levels of IgG and its isotypes were produced in mice infected with wild-type (WT) S. typhimurium or its aforementioned mutant strains. The ΔlppAB ΔmsbB mutant-immunized animals resulted in the production of higher levels of fecal IgA and serum cytokines during later stages of vaccination (adaptive response). A significant production of interleukin-6 from T-cells was also noted in the ΔlppAB ΔmsbB mutant-immunized mice when compared to that of the ΔlppAB mutant. On the other hand, IL-17A production was significantly more in the serum of ΔlppAB mutant-immunized mice (innate response) with a stronger splenic T-cell proliferative and tumor-necrosis factor-a production. Based on 2-dimensional gel analysis, alterations in the levels of several proteins were observed in both the mutant strains when compared to that in WT S. typhimurium and could be associated with the higher immunogenicity of the mutants. Finally, both ΔlppAB and ΔlppAB ΔmsbB mutants provided complete protection to immunized mice against a lethal oral challenge dose of WT S. typhimurium. Thus, these mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens.

Original languageEnglish (US)
Article number148
JournalFrontiers in cellular and infection microbiology
Volume6
Issue numberNOV
DOIs
StatePublished - Nov 10 2016

Fingerprint

Acetyltransferases
Salmonella enterica
Lipoproteins
Immunity
Immunization
Heterophile Antigens
T-Lymphocytes
Lipid A
Interleukin-17
Adaptive Immunity
Serum
Innate Immunity
Immunoglobulin A
Genes
Lipopolysaccharides
Interleukin-6
Vaccination
Vaccines
Tumor Necrosis Factor-alpha
Immunoglobulin G

Keywords

  • 2-dimensional gel electrophoresis and analysis
  • Acetyltransferase (MsbB)
  • Almonella enterica serovar Typhimurium
  • Braun or murein lipoprotein (Lpp)
  • Innate and adaptive immune responses
  • Lipopolysaccharide (LPS)
  • Mouse model of salmonellosis
  • Oral live-attenuated vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Medicine(all)
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Protective immunity elicited by oral immunization of mice with Salmonella enterica serovar typhimurium braun lipoprotein (Lpp) and acetyltransferase (MsbB) mutants. / Erova, Tatiana E.; Kirtley, Michelle L.; Fitts, Eric C.; Ponnusamy, Duraisamy; Baze, Wallace B.; Andersson, Jourdan A.; Cong, Yingzi; Tiner, Bethany L.; Sha, Jian; Chopra, Ashok.

In: Frontiers in cellular and infection microbiology, Vol. 6, No. NOV, 148, 10.11.2016.

Research output: Contribution to journalArticle

Erova, Tatiana E. ; Kirtley, Michelle L. ; Fitts, Eric C. ; Ponnusamy, Duraisamy ; Baze, Wallace B. ; Andersson, Jourdan A. ; Cong, Yingzi ; Tiner, Bethany L. ; Sha, Jian ; Chopra, Ashok. / Protective immunity elicited by oral immunization of mice with Salmonella enterica serovar typhimurium braun lipoprotein (Lpp) and acetyltransferase (MsbB) mutants. In: Frontiers in cellular and infection microbiology. 2016 ; Vol. 6, No. NOV.
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abstract = "We evaluated the extent of attenuation and immunogenicity of the ΔlppAB and ΔlppAB ΔmsbB mutants of Salmonella enterica serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100{\%} animal survival) and triggered robust innate and adaptive immune responses. Comparable levels of IgG and its isotypes were produced in mice infected with wild-type (WT) S. typhimurium or its aforementioned mutant strains. The ΔlppAB ΔmsbB mutant-immunized animals resulted in the production of higher levels of fecal IgA and serum cytokines during later stages of vaccination (adaptive response). A significant production of interleukin-6 from T-cells was also noted in the ΔlppAB ΔmsbB mutant-immunized mice when compared to that of the ΔlppAB mutant. On the other hand, IL-17A production was significantly more in the serum of ΔlppAB mutant-immunized mice (innate response) with a stronger splenic T-cell proliferative and tumor-necrosis factor-a production. Based on 2-dimensional gel analysis, alterations in the levels of several proteins were observed in both the mutant strains when compared to that in WT S. typhimurium and could be associated with the higher immunogenicity of the mutants. Finally, both ΔlppAB and ΔlppAB ΔmsbB mutants provided complete protection to immunized mice against a lethal oral challenge dose of WT S. typhimurium. Thus, these mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens.",
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AU - Kirtley, Michelle L.

AU - Fitts, Eric C.

AU - Ponnusamy, Duraisamy

AU - Baze, Wallace B.

AU - Andersson, Jourdan A.

AU - Cong, Yingzi

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AU - Sha, Jian

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