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Protective Immunity Elicited by Oral Immunization of Mice with Salmonella enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants.

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-α 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.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center Bastrop, TX, USA.Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA; Sealy Center for Vaccine Development and World Health Organisation Collaborating Center for Vaccine Research, University of Texas Medical BranchGalveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical BranchGalveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA.Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA; Sealy Center for Vaccine Development and World Health Organisation Collaborating Center for Vaccine Research, University of Texas Medical BranchGalveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical BranchGalveston, TX, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27891321

Citation

Erova, Tatiana E., et al. "Protective Immunity Elicited By Oral Immunization of Mice With Salmonella Enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants." Frontiers in Cellular and Infection Microbiology, vol. 6, 2016, p. 148.
Erova TE, Kirtley ML, Fitts EC, et al. Protective Immunity Elicited by Oral Immunization of Mice with Salmonella enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants. Front Cell Infect Microbiol. 2016;6:148.
Erova, T. E., Kirtley, M. L., Fitts, E. C., Ponnusamy, D., Baze, W. B., Andersson, J. A., Cong, Y., Tiner, B. L., Sha, J., & Chopra, A. K. (2016). Protective Immunity Elicited by Oral Immunization of Mice with Salmonella enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants. Frontiers in Cellular and Infection Microbiology, 6, 148.
Erova TE, et al. Protective Immunity Elicited By Oral Immunization of Mice With Salmonella Enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants. Front Cell Infect Microbiol. 2016;6:148. PubMed PMID: 27891321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Immunity Elicited by Oral Immunization of Mice with Salmonella enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants. AU - Erova,Tatiana E, AU - Kirtley,Michelle L, AU - Fitts,Eric C, AU - Ponnusamy,Duraisamy, AU - Baze,Wallace B, AU - Andersson,Jourdan A, AU - Cong,Yingzi, AU - Tiner,Bethany L, AU - Sha,Jian, AU - Chopra,Ashok K, Y1 - 2016/11/10/ PY - 2016/08/17/received PY - 2016/10/27/accepted PY - 2016/11/29/entrez PY - 2016/11/29/pubmed PY - 2017/9/21/medline KW - 2-dimensional gel electrophoresis and analysis KW - Salmonella enterica serovar Typhimurium KW - acetyltransferase (MsbB) KW - braun or murein lipoprotein (Lpp) KW - innate and adaptive immune responses KW - lipopolysaccharide (LPS) KW - mouse model of salmonellosis KW - oral live-attenuated vaccine SP - 148 EP - 148 JF - Frontiers in cellular and infection microbiology JO - Front Cell Infect Microbiol VL - 6 N2 - 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-α 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. SN - 2235-2988 UR - https://www.unboundmedicine.com/medline/citation/27891321/Protective_Immunity_Elicited_by_Oral_Immunization_of_Mice_with_Salmonella_enterica_Serovar_Typhimurium_Braun_Lipoprotein__Lpp__and_Acetyltransferase__MsbB__Mutants_ L2 - https://doi.org/10.3389/fcimb.2016.00148 DB - PRIME DP - Unbound Medicine ER -