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A novel approach for construction of an inactivated typhoid vaccine candidate that effectively augments both humoral and cellular immune responses

Won, Gayeon, Kim, Boram, Lee, John Hwa
Vaccine 2017 v.35 no.25 pp. 3333-3341
Salmonella Typhi, T-lymphocytes, antibacterial properties, antibodies, blood serum, cell-mediated immunity, complement, cytokines, females, genes, immune response, immunization, immunoglobulin A, immunoglobulin G, immunostimulants, mice, mutants, plasmids, rabbits, splenocytes, subcutaneous injection, typhoid fever, vaccines
Salmonella enterica serovar Typhi ghost was constructed as a vaccine candidate against typhoid fever. An asd+ plasmid pJHL187 harboring a ghost cassette comprised of PhiX 174 E lysis gene stringently controlled under the convergent promotor components and was transformed into the asd gene-deleted mutant S. Typhi Ty21a strain (STG). Twenty female BALB/c mice randomly assigned into two groups were subcutaneously vaccinated at 5weeks of age to assess immunogenic characteristics of the constructed STG. The level of serum IgG in the immunized mice was significantly increased during the observational period (P<0.001) as the mice showed the significant elevation of secretory IgA at week 6 compared to those in the non-immunized mice (P<0.05). The CD3+CD4+ T cell subpopulation in the primed splenocytes showed approximately twofold increase in the immunized group. Further, the gene expression of various immunomodulatory cytokines associated with Th-1, Th-2 and Th-17 immunity was observed in in vitro restimulated splenocytes isolated from the immunized mice. Serum Bactericidal activity of antibodies produced in the rabbits immunized with STG was proved by the elimination of almost all of wild-type S. Typhi in the presence of exogenous complement over an hour at week 6 after the first immunization. The immuno-stimulatory traits of STG demonstrated that the construct effectively enhanced the immunological responses, providing a potential of STG as the vaccine candidate against typhoid fever.