AUTHOR=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 K. 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2016.00148

DOI=10.3389/fcimb.2016.00148

ISSN=2235-2988

ABSTRACT=<p>We evaluated the extent of attenuation and immunogenicity of the Δ<italic>lppAB</italic> and Δ<italic>lppAB</italic> Δ<italic>msbB</italic> mutants of <italic>Salmonella enterica</italic> serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (<italic>lppA</italic> and <italic>lppB</italic>) or in combination with the <italic>msbB</italic> 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) <italic>S. typhimurium</italic> or its aforementioned mutant strains. The Δ<italic>lppAB</italic> Δ<italic>msbB</italic> 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 Δ<italic>lppAB</italic> Δ<italic>msbB</italic> mutant-immunized mice when compared to that of the Δ<italic>lppAB</italic> mutant. On the other hand, IL-17A production was significantly more in the serum of Δ<italic>lppAB</italic> 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 <italic>S. typhimurium</italic> and could be associated with the higher immunogenicity of the mutants. Finally, both Δ<italic>lppAB</italic> and Δ<italic>lppAB</italic> Δ<italic>msbB</italic> mutants provided complete protection to immunized mice against a lethal oral challenge dose of WT <italic>S. typhimurium</italic>. Thus, these mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens.</p>